Journal articles: 'Venom Peptide Library'

1

Wu, Xiangyue, Yan Chen, Hao Liu, Xiangjin Kong, Xinyao Liang, Yu Zhang, Cheng Tang, and Zhonghua Liu. "The Molecular Composition of Peptide Toxins in the Venom of Spider Lycosa coelestis as Revealed by cDNA Library and Transcriptomic Sequencing." Toxins 15, no. 2 (February 10, 2023): 143. http://dx.doi.org/10.3390/toxins15020143.

Full text

Abstract:

In the so-called “struggle for existence” competition, the venomous animals developed a smart and effective strategy, envenomation, for predation and defense. Biochemical analysis revealed that animal venoms are chemical pools of proteinase, peptide toxins, and small organic molecules with various biological activities. Of them, peptide toxins are of great molecular diversity and possess the capacity to modulate the activity of ion channels, the second largest group of drug targets expressed on the cell membrane, which makes them a rich resource for developing peptide drug pioneers. The spider Lycosa coelestis (L. coelestis) commonly found in farmland in China is a dominant natural enemy of agricultural pests; however, its venom composition and activity were never explored. Herein, we conducted cDNA library and transcriptomic sequencing of the venom gland of L. coelestis, which identified 1131 high-quality expressed sequence tags (ESTs), grouped into three categories denoted as toxin-like ESTs (597, 52.79%), cellular component ESTs (357, 31.56%), and non-matched ESTs (177, 15.65%). These toxin-like ESTs encode 98 non-reductant toxins, which are artificially divided into 11 families based on their sequence homology and cysteine frameworks (2–14 cysteines forming 1–7 disulfide bonds to stabilize the toxin structure). Furthermore, RP-HPLC purification combined with off-line MALDI-TOF analysis have detected 147 different peptides physically existing in the venom of L. coelestis. Electrophysiology analysis confirmed that the venom preferably inhibits the voltage-gated calcium channels in rat dorsal root ganglion neurons. Altogether, the present study has added a great lot of new members to the spider toxin superfamily and built the foundation for characterizing novel active peptides in the L. coelestis venom.

APA, Harvard, Vancouver, ISO, and other styles

2

Liao, Qingyi, Xiangjin Kong, Guoqing Luo, Xiangyue Wu, Yinping Li, Qicai Liu, Cheng Tang, and Zhonghua Liu. "Molecular Diversity of Peptide Toxins in the Venom of Spider Heteropoda pingtungensis as Revealed by cDNA Library and Transcriptome Sequencing Analysis." Toxins 14, no. 2 (February 14, 2022): 140. http://dx.doi.org/10.3390/toxins14020140.

Full text

Abstract:

The venoms of toxic animals are chemical pools composed of various proteins, peptides, and small organic molecules used for predation and defense, in which the peptidic toxins have been intensively pursued mining modulators targeting disease-related ion channels and receptors as valuable drug pioneers. In the present study, we uncovered the molecular diversity of peptide toxins in the venom of the spider Heteropoda pingtungensis (H. pingtungensis) by using a combinatory strategy of venom gland cDNA library and transcriptome sequencing (RNA-seq). An amount of 991 high-quality expressed sequence tags (ESTs) were identified from 1138 generated sequences, which fall into three categories, such as the toxin-like ESTs (531, 53.58%), the cellular component ESTs (255, 25.73%), and the no-match ESTs (205, 20.69%), as determined by gene function annotations. Of them, 190 non-redundant toxin-like peptides were identified and can be artificially grouped into 13 families based on their sequence homology and cysteine frameworks (families A–M). The predicted mature toxins contain 2–10 cysteines, which are predicted to form intramolecular disulfide bonds to stabilize their three-dimensional structures. Bioinformatics analysis showed that toxins from H. pingtungensis venom have high sequences variability and the biological targets for most toxins are unpredictable due to lack of homology to toxins with known functions in the database. Furthermore, RP-HPLC and MALDI-TOF analyses have identified a total of 110 different peptides physically existing in the H. pingtungensis venom, and many RP-HPLC fractions showed potent inhibitory activity on the heterologously expressed NaV1.7 channel. Most importantly, two novel NaV1.7 peptide antagonists, µ-Sparatoxin-Hp1 and µ-Sparatoxin-Hp2, were characterized. In conclusion, the present study has added many new members to the spider toxin superfamily and built the foundation for identifying novel modulators targeting ion channels in the H. pingtungensis venom.

APA, Harvard, Vancouver, ISO, and other styles

3

Shi, Wanxia, Pengchen He, Xian-Chun Zeng, Weiwei Wu, and Xiaoming Chen. "Inhibitory Effect of an Acidic Peptide on the Activity of an Antimicrobial Peptide from the Scorpion Mesobuthus martensii Karsch." Molecules 23, no. 12 (December 14, 2018): 3314. http://dx.doi.org/10.3390/molecules23123314.

Full text

Abstract:

Highly acidic peptides with no disulfide bridges are widely present in the scorpion venoms; however, none of them has been functionally characterized so far. Here, we cloned the full-length cDNA of a short-chain highly acidic peptide (referred to as HAP-1) from a cDNA library made from the venom glands of the Chinese scorpion Mesobuthus martensii Karsch. HAP-1 contains 19 amino acid residues with a predicted IP value of 4.25. Acidic amino residues account for 33.3% of the total residues in the molecule of HAP-1. HAP-1 shows 76–98% identities to some scorpion venom peptides that have not yet been functionally characterized. Secondary structure prediction showed that HAP-1 contains a beta-sheet region (residues 9–17), and two coiled coil regions (residues 1–8 and 18–19) located at the N-terminal and C-terminal regions of the peptide, respectively. Antimicrobial assay showed that HAP-1 does not have any effect on the growth of the bacterium Staphylococcus aureus AB94004. However, it potently inhibits the antimicrobial activity of a 13-mer peptide from M. martensii Karsch against Staphylococcus aureus AB94004. This finding is the first characterization of the function of such highly acidic peptides from scorpions.

APA, Harvard, Vancouver, ISO, and other styles

4

Kimura, Tadashi, Seigo Ono, and Tai Kubo. "Molecular Cloning and Sequence Analysis of the cDNAs Encoding Toxin-Like Peptides from the Venom Glands of Tarantula Grammostola rosea." International Journal of Peptides 2012 (February 29, 2012): 1–10. http://dx.doi.org/10.1155/2012/731293.

Full text

Abstract:

Tarantula venom glands produce a large variety of bioactive peptides. Here we present the identification of venom components obtained by sequencing clones isolated from a cDNA library prepared from the venom glands of the Chilean common tarantula, Grammostola rosea. The cDNA sequences of about 1500 clones out of 4000 clones were analyzed after selection using several criteria. Forty-eight novel toxin-like peptides (GTx1 to GTx7, and GTx-TCTP and GTx-CRISP) were predicted from the nucleotide sequences. Among these peptides, twenty-four toxins are ICK motif peptides, eleven peptides are MIT1-like peptides, and seven are ESTX-like peptides. Peptides similar to JZTX-64, aptotoxin, CRISP, or TCTP are also obtained. GTx3 series possess a cysteine framework that is conserved among vertebrate MIT1, Bv8, prokineticins, and invertebrate astakines. GTx-CRISP is the first CRISP-like protein identified from the arthropod venom. Real-time PCR revealed that the transcripts for TCTP-like peptide are expressed in both the pereopodal muscle and the venom gland. Furthermore, a unique peptide GTx7-1, whose signal and prepro sequences are essentially identical to those of HaTx1, was obtained.

APA, Harvard, Vancouver, ISO, and other styles

5

Kalogeropoulos, Konstantinos, Andreas Treschow, Ulrich auf dem Keller, Teresa Escalante, Alexandra Rucavado, José Gutiérrez, Andreas Laustsen, and Christopher Workman. "Protease Activity Profiling of Snake Venoms Using High-Throughput Peptide Screening." Toxins 11, no. 3 (March 19, 2019): 170. http://dx.doi.org/10.3390/toxins11030170.

Full text

Abstract:

Snake venom metalloproteinases (SVMPs) and snake venom serine proteinases (SVSPs) are among the most abundant enzymes in many snake venoms, particularly among viperids. These proteinases are responsible for some of the clinical manifestations classically seen in viperid envenomings, including hemorrhage, necrosis, and coagulopathies. The objective of this study was to investigate the enzymatic activities of these proteins using a high-throughput peptide library to screen for the proteinase targets of the venoms of five viperid (Echis carinatus, Bothrops asper, Daboia russelii, Bitis arietans, Bitis gabonica) and one elapid (Naja nigricollis) species of high medical importance. The proteinase activities of these venoms were each tested against 360 peptide substrates, yielding 2160 activity profiles. A nonlinear regression model that accurately described the observed enzymatic activities was fitted to the experimental data, allowing for the comparison of cleavage rates across species. In this study, previously unknown protein targets of snake venom proteinases were identified, potentially implicating novel human and animal proteins that may be involved in the pathophysiology of viper envenomings. The functional relevance of these targets was further evaluated and discussed. These new findings may contribute to our understanding of the clinical manifestations and underlying biochemical mechanisms of snakebite envenoming by viperid species.

APA, Harvard, Vancouver, ISO, and other styles

6

Hu, Zhaotun, Bo Chen, Zhen Xiao, Xi Zhou, and Zhonghua Liu. "Transcriptomic Analysis of the Spider Venom Gland Reveals Venom Diversity and Species Consanguinity." Toxins 11, no. 2 (January 24, 2019): 68. http://dx.doi.org/10.3390/toxins11020068.

Full text

Abstract:

Selenocosmia jiafu (S. jiafu) has been recently identified as a new species of spider in China. It lives in the same habitat as various other venomous spiders, including Chilobrachys jingzhao (C. jingzhao), Selenocosmia huwena (S. huwena), and Macrothele raveni (M. raveni). The venom from these different species of spiders exhibits some similarities and some differences in terms of their biochemical and electrophysiological properties. With the objective to illustrate the diversity in venom peptide toxins and to establish the evolutionary relationship between different spider species, we first performed transcriptomic analysis on a cDNA library from the venom gland of S. jiafu. We identified 146 novel toxin-like sequences, which were classified into eighteen different superfamilies. This transcriptome was then compared with that of C. jingzhao, which revealed that the putative toxins from both spider venoms may have originated from the same ancestor, although novel toxins evolved independently in the two species. A BLAST search and pharmacological analysis revealed that the two venoms have similar sodium channel modulation activity. This study provides insights into the venom of two closely related species of spider, which will prove useful towards understanding the structure and function of their toxins.

APA, Harvard, Vancouver, ISO, and other styles

7

Zhang, Kangran, Yang Liu, and Yezhong Tang. "Screening of TNFR1 Binding Peptides from Deinagkistrodon acutus Venom through Phage Display." Toxins 14, no. 2 (February 19, 2022): 155. http://dx.doi.org/10.3390/toxins14020155.

Full text

Abstract:

The venomous species Deinagkistrodon acutus has been used as anti-inflammatory medicine in China for a long time. It has been proven to have anti-inflammatory activity, but its specific anti-inflammatory components have not yet been fully elucidated. Tumor necrosis factor receptor-1 (TNFR1), which participates in important intracellular signaling pathways, mediates apoptosis, and functions as a regulator of inflammation, is often used as the target to develop anti-inflammatory drugs. The small peptides of snake venom have the advantages of weak immunogenicity and strong activity. To obtain the specific TNFR1 binding peptides, we constructed a T7 phage library of D. acutus venom glands, and then performed biopanning against TNFR1 on the constructed library. After biopanning three times, several sequences with potential binding capacity were obtained and one 41-amino acid peptide was selected through a series of biological analyses including sequence length, solubility, and simulated affinity, named DAvp-1. After synthesis, the binding capacity of DAvp-1 and TNFR1 was verified using surface plasmon resonance technology (SPR). Conclusively, by applying phage display technology, this work depicts the successful screening of a promising peptide DAvp-1 from D. acutus venom that binds to TNFR1. Additionally, our study emphasizes the usefulness of phage display technology for studies on screening natural product components.

APA, Harvard, Vancouver, ISO, and other styles

8

Bagheri-Ziari, Sedigheh, Delavar Shahbazzadeh, Soroush Sardari, Jean-Marc Sabatier, and Kamran Pooshang Bagheri. "Discovery of a New Analgesic Peptide, Leptucin, from the Iranian Scorpion, Hemiscorpius lepturus." Molecules 26, no. 9 (April 28, 2021): 2580. http://dx.doi.org/10.3390/molecules26092580.

Full text

Abstract:

Hemiscorpius lepturus scorpion stings do not induce considerable pain based on epidemiological surveys conducted in the southwest part of Iran. Accordingly, this study was aimed to identify the analgesic molecule in H. lepturus venom by analyzing a cDNA library of the scorpion venom gland looking for sequences having homology with known animal venom analgesic peptides. The analgesic molecule is a cysteine rich peptide of 55 amino acids. the synthetic peptide was deprotected and refolded. RP-HPLC, Ellman’s, and DLS assays confirmed the refolding accuracy. Circular dichroism (CD) showed helix and beta sheet contents. This peptide, called leptucin, demonstrated 95% analgesic activity at the dose of 0.48 mg/kg in hot plate assay. Leptucin at the doses of 0.32, 0.48, and 0.64 mg/kg showed 100% activity in thermal tail flick test. No hemolysis or cytotoxicity was observed at 8 and 16 μg. Histopathology evaluations indicated no hepatotoxicity, nephrotoxicity, and cardiotoxicity. We thus report that leptucin is the analgesic agent of H. lepturus venom. Regarding the high in vivo efficacy of leptucin and the fact it shows no observable toxicity, it could be suggested as a drug lead in a preclinical study of acute pain as well as the study of its mechanism of action.

APA, Harvard, Vancouver, ISO, and other styles

9

Rajesh, R. P., Jayaseelan B. Franklin, Iffath Badsha, P. Arjun, Ruchi P. Jain, M. S. Vignesh, and Rajesh R. Kannan. "Proteome Based de novo Sequencing of Novel Conotoxins from Marine Molluscivorous Cone Snail Conus amadis and Neurological Activities of Its Natural Venom in Zebrafish Model." Protein & Peptide Letters 26, no. 11 (October 24, 2019): 819–33. http://dx.doi.org/10.2174/0929866526666190614144006.

Full text

Abstract:

Background: Conus amadis is a carnivorous snail found abundantly in coastal waters of India. Despite its abundance in southern coastal waters of India and the fact that most of the conotoxin act in neuronal system, research work on Conus amadis venom was not much focused. So we have made a brief study on the venom complex of Conus amadis to identify the library of novel conotoxins and to screen the natural venom for neurological function. Objective: De novo sequencing of novel conopeptides from the venom cocktail of Conus amadis and to screen its natural venom for the presence of biological activities in zebrafish model. Methods: Proteome based MALDI-TOF and LC-MS-MS analysis for identification of novel conotoxins and subsequent sequencing. Due to the complex disulfide rich nature of the venom peptides, the study also involves global chemical modification experiments of the venom extract to unambiguously determine the sequence of novel conotoxins. Biological function analysis of natural venom was tested in zebrafish model to ascertain anti-epileptic properties. Results: In this study, we have identified 19 novel conotoxins containing 1, 2 & 3 disulfides, belonging to different classes. Among them, 2 novel contryphans, 3 T-superfamily conotoxins, 2 A-superfamily conotoxins and 2 Mini M-Superfamily conotoxins were sequenced to its amino acid level from the fragmented spectrum of singly and doubly charged parent ions using de novo sequencing strategies. ama1054, a contryphan peptide toxin, possesses post translationally modified bromo tryptophan at its seventh position. Except ama1251, all the sequenced peptide toxins possess modified C-terminal amidation. Crude venom exhibited anticonvulsant properties in pentylenetetrazole-induced seizure in zebrafish larvae, which suggested anti-epileptic property of the venom cocktail. Acetylcholinesterase activity was also identified in the venom complex. Conclusion: Based on the preliminary evidence, if this study is extended further through bioassay guided purification, could possibly yield peptide toxins with anticonvulsant and other neurologically active molecules.

APA, Harvard, Vancouver, ISO, and other styles

10

Ji, Mengyao, Tengyu Zhu, Meichen Xing, Ning Luan, James Mwangi, Xiuwen Yan, Guoxiang Mo, et al. "An Antiviral Peptide from Alopecosa nagpag Spider Targets NS2B–NS3 Protease of Flaviviruses." Toxins 11, no. 10 (October 10, 2019): 584. http://dx.doi.org/10.3390/toxins11100584.

Full text

Abstract:

Flaviviruses are single-stranded RNA viruses predominantly transmitted by the widely distributed Aedes mosquitoes in nature. As important human pathogens, the geographic reach of Flaviviruses and their threats to public health are increasing, but there is currently no approved specific drug for treatment. In recent years, the development of peptide antivirals has gained much attention. Natural host defense peptides which uniquely evolved to protect the hosts have been shown to have antiviral properties. In this study, we firstly collected the venom of the Alopecosa nagpag spider from Shangri-La County, Yunnan Province. A defense peptide named Av-LCTX-An1a (Antiviral-Lycotoxin-An1a) was identified from the spider venom, and its anti-dengue serotype-2 virus (DENV2) activity was verified in vitro. Moreover, a real-time fluorescence-based protease inhibition assay showed that An1a functions as a DENV2 NS2B–NS3 protease inhibitor. Furthermore, we also found that An1a restricts zika virus (ZIKV) infection by inhibiting the ZIKV NS2B–NS3 protease. Together, our findings not only demonstrate that An1a might be a candidate for anti-flavivirus drug but also indicate that spider venom is a potential resource library rich in antiviral precursor molecules.

APA, Harvard, Vancouver, ISO, and other styles

11

Ye, Xiangdong, Xin Liu, Xudong Luo, Fang Sun, Chenhu Qin, Li Ding, Wen Zhu, Huajun Zhang, Haimei Zhou, and Zongyun Chen. "Characterization of the Molecular Diversity and Degranulation Activity of Mastoparan Family Peptides from Wasp Venoms." Toxins 15, no. 5 (May 12, 2023): 331. http://dx.doi.org/10.3390/toxins15050331.

Full text

Abstract:

Wasp stings have become an increasingly serious public health problem because of their high incidence and mortality rates in various countries and regions. Mastoparan family peptides are the most abundant natural peptides in hornet venoms and solitary wasp venom. However, there is a lack of systematic and comprehensive studies on mastoparan family peptides from wasp venoms. In our study, for the first time, we evaluated the molecular diversity of 55 wasp mastoparan family peptides from wasp venoms and divided them into four major subfamilies. Then, we established a wasp peptide library containing all 55 known mastoparan family peptides by chemical synthesis and C-terminal amidation modification, and we systematically evaluated their degranulation activities in two mast cell lines, namely the RBL-2H3 and P815 cell lines. The results showed that among the 55 mastoparans, 35 mastoparans could significantly induce mast cell degranulation, 7 mastoparans had modest mast cell degranulation activity, and 13 mastoparans had little mast cell degranulation activity, suggesting functional variation in mastoparan family peptides from wasp venoms. Structure–function relationship studies found that the composition of amino acids in the hydrophobic face and amidation in the C-terminal region are critical for the degranulation activity of mastoparan family peptides from wasp venoms. Our research will lay a theoretical foundation for studying the mechanism underlying the degranulation activity of wasp mastoparans and provide new evidence to support the molecular design and molecular optimization of natural mastoparan peptides from wasp venoms in the future.

APA, Harvard, Vancouver, ISO, and other styles

12

RUDENKO, S. V., and E. E. NIPOT. "Protection by chlorpromazine, albumin and bivalent cations against haemolysis induced by melittin, [Ala-14]melittin and whole bee venom." Biochemical Journal 317, no. 3 (August 1, 1996): 747–54. http://dx.doi.org/10.1042/bj3170747.

Full text

Abstract:

The ability of the peptides melittin, [Ala-14]melittin (P14A) and whole bee venom to lyse red blood cells (RBC) and to cause shape transformation, binding, partitioning and changes in volume of the cells during haemolysis, as well as the action of the bivalent cations Zn2+ and Ca2+, chlorpromazine, albumin and plasma on the peptide-induced haemolysis of RBC in high ionic-strength solution, have been investigated. The protective effect of all inhibitors depends on whether they have been added to the media before or after the cells. When added before the cells they reduced significantly the rate of peptide-induced haemolysis and shape transformation. The effect was maximal when agents acted simultaneously after introduction of the cells into the media containing both inhibitors and peptides. Incubation of the cells in isotonic solution before the addition of peptides enhanced 2–3-fold the RBC susceptibility (i.e. rate of haemolysis) to lytic action of the same amount of peptides, and increased the order of the haemolytic reaction, although the power law coefficient did not exceed a value of 2 for all peptides, suggesting that haemolysis is attributable to the monomeric or dimeric forms of the peptides. Partition coefficients were of the order of ∼106 M-1, and P14A possessed a value 3-fold larger compared with melittin and bee venom, which correlated with its enhanced haemolytic activity. The protective action of inhibitors against peptide-induced haemolysis has been explained on the basis of their ability to compete with peptide binding at an early stage of peptide–membrane interaction, and not as a result of inhibition of a pre-existing peptide-induced pore. Whereas melittin increased the volume of RBC during haemolysis, P14A, melittin in the presence of phospholipase A2 or bee venom, reduced the volume in a concentration-dependent manner. The present data reveal the significant role of the initial stage of peptide–membrane interaction and peptide structure in the mechanism of haemolysis. These data are not consistent with a lipid-based mechanism of peptide-induced haemolysis, indicating that the mode of peptide–protein interaction is an important and decisive step in the haemolytic mechanism. It should be noted that data (in the form of three additional Tables) on the ability of inhibitors to protect cells from haemolysis when inhibitor and peptide act simultaneously are available. They are reported in Supplementary Publication SUP 50178, which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1996) 313, 9.

APA, Harvard, Vancouver, ISO, and other styles

13

Zhao, Zhenhuan, Yibao Ma, Chao Dai, Ruiming Zhao, SongRyong Li, Yingliang Wu, Zhijian Cao, and Wenxin Li. "Imcroporin, a New Cationic Antimicrobial Peptide from the Venom of the Scorpion Isometrus maculates." Antimicrobial Agents and Chemotherapy 53, no. 8 (May 18, 2009): 3472–77. http://dx.doi.org/10.1128/aac.01436-08.

Full text

Abstract:

ABSTRACT The pace of resistance against antibiotics almost exceeds that of the development of new drugs. As many bacteria have become resistant to conventional antibiotics, new drugs or drug resources are badly needed to combat antibiotic-resistant pathogens, like methicillin-resistant Staphylococcus aureus (MRSA). Antimicrobial peptides, rich sources existing in nature, are able to effectively kill multidrug-resistant pathogens. Here, imcroporin, a new antimicrobial peptide, was screened and isolated from the cDNA library of the venomous gland of Isometrus maculates. The MIC of imcroporin against MRSA was 50 μg/ml, 8-fold lower than that of cefotaxime and 40-fold lower than that of penicillin. Imcroporin killed bacteria rapidly in vitro, inhibited bacterial growth, and cured infected mice. These results revealed that imcroporin could be considered a potential anti-infective drug or lead compound, especially for treating antibiotic-resistant pathogens.

APA, Harvard, Vancouver, ISO, and other styles

14

Li, Fengjiao, Saizhi Wu, Ninglin Chen, Jingyu Zhu, Xinxin Zhao, Peng Zhang, Youlin Zeng, and Zhonghua Liu. "Fatty Acid Modification of the Anticancer Peptide LVTX-9 to Enhance Its Cytotoxicity against Malignant Melanoma Cells." Toxins 13, no. 12 (December 4, 2021): 867. http://dx.doi.org/10.3390/toxins13120867.

Full text

Abstract:

Spider venom is a valuable resource for the development of novel anticancer drugs. In this study, we focused on novel linear amphipathic α-helical anticancer peptide LVTX-9, which was derived from the cDNA library of the venom gland of the spider Lycosa vittata. The cytotoxicity of LVTX-9 against murine melanoma cells in the range of 1.56–200 μM was tested and found to be significantly lower than those of most anticancer peptides reported. Its IC50 was determined to be 59.2 ± 19.8 μM in a serum or 76.3 ± 12.7 μM in serum-free medium. Fatty acid modification is a promising strategy for improving peptide performance. Therefore, to enhance the cytotoxic activity of LVTX-9, fatty acid modification of this peptide was performed, and five different carbon chain length lipopeptides named LVTX-9-C12-C20 were produced. Among them, the lipopeptide LVTX-9-C18 showed the highest cytotoxic activity in relation to B16-F10 cells, whether in a serum or serum-free medium. Most importantly, the cytotoxic activity of LVTX-9-C18 was improved by about 12.9 times in a serum medium or 19.3 times in a serum-free medium compared to that of LVTX-9. Subsequently, assays including scanning electron microscopy, trypan blue staining, lactate dehydrogenase leakage assay, and hemolytic activity could indicate that the potential direct cell membrane disruption is the main mechanism of LVTX-9-C18 to induce cancer cell death. Furthermore, the LVTX-9-C18 also showed strong cytotoxicity in relation to 3D B16-F10 spheroids, which indicates it might be a promising lead for developing anticancer drugs.

APA, Harvard, Vancouver, ISO, and other styles

15

Kazemi-Lomedasht, Fatemeh, Fatemeh Rahimi Jamnani, Mahdi Behdani, and Delavar Shahbazzadeh. "Linear mimotope analysis of Iranian cobra (Naja oxiana) snake venom using peptide displayed phage library." Toxin Reviews 38, no. 2 (January 5, 2018): 106–14. http://dx.doi.org/10.1080/15569543.2017.1420082.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

da Silveira, Rafael B., Ana C. M. Wille, Olga M. Chaim, Marcia H. Appel, Dilza T. Silva, Célia R. C. Franco, Leny Toma, et al. "Identification, cloning, expression and functional characterization of an astacin-like metalloprotease toxin from Loxosceles intermedia (brown spider) venom." Biochemical Journal 406, no. 2 (August 13, 2007): 355–63. http://dx.doi.org/10.1042/bj20070363.

Full text

Abstract:

Injuries caused by brown spiders (Loxosceles genus) are associated with dermonecrotic lesions with gravitational spreading and systemic manifestations. The venom has a complex composition containing many different toxins, of which metalloproteases have been described in many different species of this genus. These toxins may degrade extracellular matrix constituents acting as a spreading factor. By using a cDNA library from an Loxosceles intermedia venom gland, we cloned and expressed a 900 bp cDNA, which encoded a signal peptide and a propeptide, which corresponded to a 30 kDa metalloprotease, now named LALP (Loxosceles astacin-like protease). Recombinant LALP was refolded and used to produce a polyclonal antiserum, which showed cross-reactivity with a 29 kDa native venom protein. CD analysis provided evidence that the recombinant LALP toxin was folded correctly, was still in a native conformation and had not aggregated. LALP addition to endothelial cell cultures resulted in de-adhesion of the cells, and also in the degradation of fibronectin and fibrinogen (this could be inhibited by the presence of the bivalent chelator 1,10-phenanthroline) and of gelatin in vitro. Sequence comparison (nucleotide and deduced amino acid), phylogenetic analysis and analysis of the functional recombinant toxin revealed that LALP is related in both structure and function to the astacin family of metalloproteases. This suggests that an astacin-like toxin is present in a animal venom secretion and indicates that recombinant LALP will be a useful tool for future structural and functional studies on venom and the astacin family.

APA, Harvard, Vancouver, ISO, and other styles

17

Kalina, Rimma S., Igor E. Kasheverov, Sergey G. Koshelev, Oksana V. Sintsova, Steve Peigneur, Ernesto Lopes Pinheiro-Junior, Roman S. Popov, et al. "Nicotinic Acetylcholine Receptors Are Novel Targets of APETx-like Toxins from the Sea Anemone Heteractis magnifica." Toxins 14, no. 10 (October 11, 2022): 697. http://dx.doi.org/10.3390/toxins14100697.

Full text

Abstract:

The nicotinic acetylcholine receptors (nAChRs) are prototypical ligand-gated ion channels, provide cholinergic signaling, and are modulated by various venom toxins and drugs in addition to neurotransmitters. Here, four APETx-like toxins, including two new toxins, named Hmg 1b-2 Metox and Hmg 1b-5, were isolated from the sea anemone Heteractis magnifica and characterized as novel nAChR ligands and acid-sensing ion channel (ASIC) modulators. All peptides competed with radiolabeled α-bungarotoxin for binding to Torpedo californica muscle-type and human α7 nAChRs. Hmg 1b-2 potentiated acetylcholine-elicited current in human α7 receptors expressed in Xenopus laevis oocytes. Moreover, the multigene family coding APETx-like peptides library from H. magnifica was described and in silico surface electrostatic potentials of novel peptides were analyzed. To explain the 100% identity of some peptide isoforms between H. magnifica and H. crispa, 18S rRNA, COI, and ITS analysis were performed. It has been shown that the sea anemones previously identified by morphology as H. crispa belong to the species H. magnifica.

APA, Harvard, Vancouver, ISO, and other styles

18

HOWARD, Linda, Xiaohong LU, Sally MITCHELL, Susan GRIFFITHS, and Paul GLYNN. "Molecular cloning of MADM: a catalytically active mammalian disintegrin-metalloprotease expressed in various cell types." Biochemical Journal 317, no. 1 (July 1, 1996): 45–50. http://dx.doi.org/10.1042/bj3170045.

Full text

Abstract:

A peptide sequence of a metalloprotease purified from bovine brain [Chantry, Gregson and Glynn (1989) J. Biol. Chem. 264, 21603–21607] was used to design an oligonucleotide probe for screening a bovine brain cDNA library. A contig of the two overlapping cDNA clones that were isolated encoded a 748-amino-acid polypeptide with similarity to the disintegrin–metalloprotease precursor proteins of haemorrhagic snake venom. The bovine protein has been named MADM, for mammalian disintegrin–metalloprotease. The predicted mature protein has 534 amino acids arrayed as extracellular metalloprotease and disintegrin (potential integrin-binding) domains, a transmembrane helix and a basic/proline-rich cytoplasmic C-terminus. Highly conserved homologues of bovine MADM were found in cDNA libraries of rat brain and a human U937 histiocytic lymphoma cell line. A wide variety of mammalian cell lines expressed low levels of MADM mRNA (4.5 and 3.2 kb transcripts) and mature polypeptide (Mr 62000), as assessed by Northern analysis and Western blotting with an antiserum raised to a peptide within the disintegrin domain. MADM appears to be a rather distantly related member of the reprolysin protein family, which includes both the snake venom disintegrin–metalloproteases and a number of predicted cell-surface disintegrin-containing mammalian proteins.

APA, Harvard, Vancouver, ISO, and other styles

19

Herzig, Volker, Yong-Cyuan Chen, Yanni K. Y. Chin, Zoltan Dekan, Yu-Wang Chang, Hui-Ming Yu, Paul F. Alewood, Chien-Chang Chen, and Glenn F. King. "The Tarantula Toxin ω-Avsp1a Specifically Inhibits Human CaV3.1 and CaV3.3 via the Extracellular S3-S4 Loop of the Domain 1 Voltage-Sensor." Biomedicines 10, no. 5 (May 4, 2022): 1066. http://dx.doi.org/10.3390/biomedicines10051066.

Full text

Abstract:

Inhibition of T-type calcium channels (CaV3) prevents development of diseases related to cardiovascular and nerve systems. Further, knockout animal studies have revealed that some diseases are mediated by specific subtypes of CaV3. However, subtype-specific CaV3 inhibitors for therapeutic purposes or for studying the physiological roles of CaV3 subtypes are missing. To bridge this gap, we employed our spider venom library and uncovered that Avicularia spec. (“Amazonas Purple”, Peru) tarantula venom inhibited specific T-type CaV channel subtypes. By using chromatographic and mass-spectrometric techniques, we isolated and sequenced the active toxin ω-Avsp1a, a C-terminally amidated 36 residue peptide with a molecular weight of 4224.91 Da, which comprised the major peak in the venom. Both native (4.1 μM) and synthetic ω-Avsp1a (10 μM) inhibited 90% of CaV3.1 and CaV3.3, but only 25% of CaV3.2 currents. In order to investigate the toxin binding site, we generated a range of chimeric channels from the less sensitive CaV3.2 and more sensitive CaV3.3. Our results suggest that domain-1 of CaV3.3 is important for the inhibitory effect of ω-Avsp1a on T-type calcium channels. Further studies revealed that a leucine of T-type calcium channels is crucial for the inhibitory effect of ω-Avsp1a.

APA, Harvard, Vancouver, ISO, and other styles

20

LEDUC, Mireille, and Cassian BON. "Cloning of subunits of convulxin, a collagen-like platelet-aggregating protein from Crotalus durissus terrificus venom." Biochemical Journal 333, no. 2 (July 15, 1998): 389–93. http://dx.doi.org/10.1042/bj3330389.

Full text

Abstract:

Convulxin (CVX) is a potent platelet-aggregating glycoprotein from the venom of the snake Crotalus durissus terrificus. It consists of two subunits, α and β, joined by disulphide bridges in a hexameric structure. A cDNA library from venom gland was constructed in the vector pT3T7. The cloned cDNAs encoding the two chains of CVX were sequenced. Both are preceded by an identical 23-amino acid peptide signal sequence and encode sequences of 135 amino acids for the α chain and 125 amino acids for the β chain. These polypeptides include a carbohydrate-recognition domain (CRD) in which some of the specific amino acids required for binding Ca2+ and galactose or mannose are absent. The presence of such a domain means that CVX can be included in the family of C-type lectins along with other snake venom proteins, although it is not a true lectin. Assuming that the localization of intracatenary disulphide bridges of each CVX chain is similar to that of the CRD and that an intercatenary bridge between the α and β chains is similar to that of the C-type lectin botrocetin, we postulate the existence of an additional intercatenary bridge, which explains the tridimeric structure (αβ)3 of CVX.

APA, Harvard, Vancouver, ISO, and other styles

21

Khanongnoi, Jirawat, Siratcha Phanthong, Onrapak Reamtong, Anchalee Tungtronchitr, Wanpen Chaicumpa, and Nitat Sookrung. "Human Monoclonal scFvs that Neutralize Fribrinogenolytic Activity of Kaouthiagin, a Zinc-Metalloproteinase in Cobra (Naja kaouthia) Venom." Toxins 10, no. 12 (December 3, 2018): 509. http://dx.doi.org/10.3390/toxins10120509.

Full text

Abstract:

Snake venom-metalloproteinases (SVMPs) are the primary factors that disturb hemostasis and cause hemorrhage in the venomous snake bitten subjects. Kaouthiagin is a unique SVMP that binds and cleaves von Willebrand factor (vWF) at a specific peptide bond leading to inhibition of platelet aggregation, which enhances the hemorrhage. Kaouthiagin is a low abundant venom component of Thai cobra (Naja kaouthia); thus, most horse-derived antivenins used for cobra bite treatment do not contain adequate anti-kaouthiagin. This study aimed to produce human single-chain antibody variable fragments (HuscFvs) that bind to and interfere with kaouthiagin activity for further clinical use. Kaouthiagin was purified from N. kaouthia-holovenom by a single-step gel-filtration chromatography. The purified venom component was used in phage-biopanning to select the kaouthiagin-bound HuscFv-displayed-phage clones from a HuscFv-phage display library. The selected phages were used to infect Escherichia coli bacteria. Soluble HuscFvs expressed by three phage-transformed-E. coli clones interfered with cobra kaouthiagin binding to human vWF. Computerized simulation indicated that HuscFv of two phage-transformed E. coli clones formed contact interface with kaouthiagin residues at or near catalytic site and effectively inhibited fibrinogenolytic activity of the kaouthiagin. The HuscFvs have therapeutic potential as an adjunct of antivenins in treatment of bleeding caused by venomous snakebites.

APA, Harvard, Vancouver, ISO, and other styles

22

Bertholim, Luciana, André Zelanis, Ana K. Oliveira, and Solange M. T. Serrano. "Proteome-derived peptide library for the elucidation of the cleavage specificity of HF3, a snake venom metalloproteinase." Amino Acids 48, no. 5 (March 29, 2016): 1331–35. http://dx.doi.org/10.1007/s00726-016-2218-z.

Full text

APA, Harvard, Vancouver, ISO, and other styles

23

Van Vaerenbergh, Matthias, Griet Debyser, Bart Devreese, and Dirk C. de Graaf. "Exploring the hidden honeybee (Apis mellifera) venom proteome by integrating a combinatorial peptide ligand library approach with FTMS." Journal of Proteomics 99 (March 2014): 169–78. http://dx.doi.org/10.1016/j.jprot.2013.04.039.

Full text

APA, Harvard, Vancouver, ISO, and other styles

24

Au, L. C., S. B. Lin, J. S. Chou, G. W. Teh, K. J. Chang, and C. M. Shih. "Molecular cloning and sequence analysis of the cDNA for ancrod, a thrombin-like enzyme from the venom of Calloselasma rhodostoma." Biochemical Journal 294, no. 2 (September 1, 1993): 387–90. http://dx.doi.org/10.1042/bj2940387.

Full text

Abstract:

The 1.54 kb cDNA for ancrod, a thrombin-like enzyme, was cloned from a lambda ZAP cDNA library derived from the venom glands of Calloselasma (Agkistrodon) rhodostoma. The cDNA sequence reveals that ancrod is synthesized as a pre-zymogen of 258 amino acids, including a putative secretory peptide of 18 amino acids and a proposed zymogen peptide of 6 amino-acid residues. The amino-acid sequence of the predicted active form of the enzyme exhibits a high degree of sequence similarity to those of mammalian serine proteases (trypsin and pancreatic kallikrein) and other thrombin-like enzymes (batroxobin and flavoxobin). Key amino-acid residues (His43, Asp88, Ser182 and Asp176) that are thought to be involved in the substrate cleavage and in the substrate-binding reaction are conserved. Ancrod contains 13 cysteine residues. Based on alignment with the amino-acid sequences of trypsin and batroxobin, six disulphide bridges can be predicted to be present in the ancrod protein. The existence of a free cysteine, which changes the common sequence surrounding the Ser182 active site from Gly-Asp-Ser-Gly-Gly-Pro to Cys-Asp-Ser-Gly-Gly-Pro, is unusual for a serine protease.

APA, Harvard, Vancouver, ISO, and other styles

25

Liu, Yuan, Yaqin Tang, Xing Tang, Mengqi Wu, Shengjie Hou, Xiaohua Liu, Jing Li, Meichun Deng, Shuaiqin Huang, and Liping Jiang. "Anti-Toxoplasma gondii Effects of a Novel Spider Peptide XYP1 In Vitro and In Vivo." Biomedicines 9, no. 8 (August 1, 2021): 934. http://dx.doi.org/10.3390/biomedicines9080934.

Full text

Abstract:

Toxoplasmosis, caused by an obligate intracellular parasite Toxoplasma gondii, is one of the most prevalent zoonoses worldwide. Treatments for this disease by traditional drugs have shown numerous side effects, thus effective alternative anti-Toxoplasma strategies or drugs are urgently needed. In this study, a novel spider peptide, XYP1, was identified from the cDNA library of the venom gland of the spider Lycosa coelestis. Our results showed that XYP1 has potent anti-Toxoplasma activity in vitro and in vivo. Specifically, treatment with XYP1 significantly inhibited the viability, invasion and proliferation of tachyzoites with low cytotoxicity (IC50 = 38.79 μΜ) on human host cells, and increased the survival rate of mice acutely infected with T. gondii. Next, scanning electron microscopy, transmission electron microscopy and RNA sequencing were employed to further explore the functional mechanism of XYP1, and the results indicated that XYP1 causes membrane perforation, swelling and disruption of tachyzoites, which could be closely associated with differential expression of several membrane-associated proteins including HSP29. In conclusion, XYP1 may be a promising new drug candidate for the treatment of toxoplasmosis.

APA, Harvard, Vancouver, ISO, and other styles

26

Zhang, Peng, Yujie Yan, Junting Wang, Xiaoping Dong, Gaihua Zhang, Yong Zeng, and Zhonghua Liu. "An Anti-Cancer Peptide LVTX-8 Inhibits the Proliferation and Migration of Lung Tumor Cells by Regulating Causal Genes’ Expression in p53-Related Pathways." Toxins 12, no. 6 (June 2, 2020): 367. http://dx.doi.org/10.3390/toxins12060367.

Full text

Abstract:

Spider venom has been found to show its anticancer activity in a variety of human malignancies, including lung cancer. In this study, we investigated the anti-cancer peptide toxin LVTX-8, with linear amphipathic alpha-helical conformation, designed and synthesized from the cDNA library of spider Lycosa vittata. Multiple cellular methods, such as CCK-8 assay, flow cytometry, colony formation assay, Transwell invasion and migration assay, were performed to detect peptide-induced cell growth inhibition and anti-metastasis in lung cancer cells. Our results demonstrated that LVTX-8 displayed strong cytotoxicity and anti-metastasis towards lung cancer in vitro. Furthermore, LVTX-8 could suppress the growth and metastasis of lung cancer cells (A549 and H460) in nude mouse models. Transcriptomics, integrated with multiple bioinformatics analysis, suggested that the molecular basis of the LVTX-8-mediated inhibition of cancer cell growth and metastasis manifested in two aspects: Firstly, it could restrain the activity of cancer cell division and migration through the functional pathways, including “p53 hypoxia pathway” and “integrin signaling”. Secondly, it could regulate the expression level of apoptotic-related proteins, which may account for programmed apoptosis of cancer cells. Taken together, as an anticancer peptide with high efficiency and acceptable specificity, LVTX-8 may become a potential precursor of a therapeutic agent for lung cancer in the future.

APA, Harvard, Vancouver, ISO, and other styles

27

Calvete, Juan J., Elisa Fasoli, Libia Sanz, Egisto Boschetti, and Pier Giorgio Righetti. "Exploring the Venom Proteome of the Western Diamondback Rattlesnake,Crotalus atrox, via Snake Venomics and Combinatorial Peptide Ligand Library Approaches." Journal of Proteome Research 8, no. 6 (June 5, 2009): 3055–67. http://dx.doi.org/10.1021/pr900249q.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Fasoli, Elisa, Libia Sanz, Simon Wagstaff, Robert A. Harrison, Pier Giorgio Righetti, and Juan J. Calvete. "Exploring the venom proteome of the African puff adder, Bitis arietans, using a combinatorial peptide ligand library approach at different pHs." Journal of Proteomics 73, no. 5 (March 2010): 932–42. http://dx.doi.org/10.1016/j.jprot.2009.12.006.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Van Vaerenbergh, Matthias, Griet Debyser, Guy Smagghe, Bart Devreese, and Dirk C. de Graaf. "Unraveling the venom proteome of the bumblebee (Bombus terrestris) by integrating a combinatorial peptide ligand library approach with FT-ICR MS." Toxicon 102 (August 2015): 81–88. http://dx.doi.org/10.1016/j.toxicon.2013.10.002.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

Jahdasani, Roghaye, Fatemeh Rahimi Jamnani, Mahdi Behdani, Mahdi Habibi-Anbouhi, Najmeh Yardehnavi, Delavar Shahbazzadeh, and Fatemeh Kazemi-Lomedasht. "Identification of the immunogenic epitopes of the whole venom component of the Hemiscorpius lepturus scorpion using the phage display peptide library." Toxicon 124 (December 2016): 83–93. http://dx.doi.org/10.1016/j.toxicon.2016.11.247.

Full text

APA, Harvard, Vancouver, ISO, and other styles

31

Neff, Robert A., Mack Flinspach, Alan Gibbs, Amy Y. Shih, Natali A. Minassian, Yi Liu, Ross Fellows, et al. "Comprehensive engineering of the tarantula venom peptide huwentoxin-IV to inhibit the human voltage-gated sodium channel hNav1.7." Journal of Biological Chemistry 295, no. 5 (December 23, 2019): 1315–27. http://dx.doi.org/10.1074/jbc.ra119.011318.

Full text

Abstract:

Pain is a significant public health burden in the United States, and current treatment approaches rely heavily on opioids, which often have limited efficacy and can lead to addiction. In humans, functional loss of the voltage-gated sodium channel Nav1.7 leads to pain insensitivity without deficits in the central nervous system. Accordingly, discovery of a selective Nav1.7 antagonist should provide an analgesic without abuse liability and an improved side-effect profile. Huwentoxin-IV, a component of tarantula venom, potently blocks sodium channels and is an attractive scaffold for engineering a Nav1.7-selective molecule. To define the functional impact of alterations in huwentoxin-IV sequence, we produced a library of 373 point mutants and tested them for Nav1.7 and Nav1.2 activity. We then combined favorable individual changes to produce combinatorial mutants that showed further improvements in Nav1.7 potency (E1N, E4D, Y33W, Q34S–Nav1.7 pIC50 = 8.1 ± 0.08) and increased selectivity over other Nav isoforms (E1N, R26K, Q34S, G36I, Nav1.7 pIC50 = 7.2 ± 0.1, Nav1.2 pIC50 = 6.1 ± 0.18, Nav1.3 pIC50 = 6.4 ± 1.0), Nav1.4 is inactive at 3 μm, and Nav1.5 is inactive at 10 μm. We also substituted noncoded amino acids at select positions in huwentoxin-IV. Based on these results, we identify key determinants of huwentoxin's Nav1.7 inhibition and propose a model for huwentoxin-IV's interaction with Nav1.7. These findings uncover fundamental features of huwentoxin involved in Nav1.7 blockade, provide a foundation for additional optimization of this molecule, and offer a basis for the development of a safe and effective analgesic.

APA, Harvard, Vancouver, ISO, and other styles

32

Guo, Guoning, Yuliang Cao, Guoyan Zhu, Zhu Tian, Yajun Gou, Cong Chen, and Minghua Liu. "Screening, tandem expression and immune activity appraisal of Deinagkistrodon acutus (pit viper) venom mimotopes from a phage display 12-mer peptide library." Biotechnology Letters 38, no. 11 (July 15, 2016): 1867–73. http://dx.doi.org/10.1007/s10529-016-2172-6.

Full text

APA, Harvard, Vancouver, ISO, and other styles

33

Kleiz-Ferreira, Jessica Matos, Hans Bernaerts, Ernesto Lopes Pinheiro-Junior, Steve Peigneur, Russolina Benedeta Zingali, and Jan Tytgat. "Pharmacological Screening of Venoms from Five Brazilian Micrurus Species on Different Ion Channels." International Journal of Molecular Sciences 23, no. 14 (July 13, 2022): 7714. http://dx.doi.org/10.3390/ijms23147714.

Full text

Abstract:

Coral snake venoms from the Micrurus genus are a natural library of components with multiple targets, yet are poorly explored. In Brazil, 34 Micrurus species are currently described, and just a few have been investigated for their venom activities. Micrurus venoms are composed mainly of phospholipases A2 and three-finger toxins, which are responsible for neuromuscular blockade—the main envenomation outcome in humans. Beyond these two major toxin families, minor components are also important for the global venom activity, including Kunitz-peptides, serine proteases, 5′ nucleotidases, among others. In the present study, we used the two-microelectrode voltage clamp technique to explore the crude venom activities of five different Micrurus species from the south and southeast of Brazil: M. altirostris, M. corallinus, M. frontalis, M. carvalhoi and M. decoratus. All five venoms induced full inhibition of the muscle-type α1β1δε nAChR with different levels of reversibility. We found M. altirostris and M. frontalis venoms acting as partial inhibitors of the neuronal-type α7 nAChR with an interesting subsequent potentiation after one washout. We discovered that M. altirostris and M. corallinus venoms modulate the α1β2 GABAAR. Interestingly, the screening on KV1.3 showed that all five Micrurus venoms act as inhibitors, being totally reversible after the washout. Since this activity seems to be conserved among different species, we hypothesized that the Micrurus venoms may rely on potassium channel inhibitory activity as an important feature of their envenomation strategy. Finally, tests on NaV1.2 and NaV1.4 showed that these channels do not seem to be targeted by Micrurus venoms. In summary, the venoms tested are multifunctional, each of them acting on at least two different types of targets.

APA, Harvard, Vancouver, ISO, and other styles

34

Chenbang, M., L. Wang, M. Zhou, T. Chen, and C. Shaw. "Molecular cloning of the helokinestatin/CNP precursor from a venom-derived cDNA library of the Mexican beaded lizard, Heloderma horridum, and identification of a novel encoded bradykinin-antagonist peptide, helokinestatin-6." Regulatory Peptides 164, no. 1 (September 2010): 51. http://dx.doi.org/10.1016/j.regpep.2010.07.160.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Mansbach, Rachael A., Srirupa Chakraborty, Timothy Travers, and S. Gnanakaran. "Graph-Directed Approach for Downselecting Toxins for Experimental Structure Determination." Marine Drugs 18, no. 5 (May 14, 2020): 256. http://dx.doi.org/10.3390/md18050256.

Full text

Abstract:

Conotoxins are short, cysteine-rich peptides of great interest as novel therapeutic leads and of great concern as lethal biological agents due to their high affinity and specificity for various receptors involved in neuromuscular transmission. Currently, of the approximately 6000 known conotoxin sequences, only about 3% have associated structural characterization, which leads to a bottleneck in rapid high-throughput screening (HTS) for identification of potential leads or threats. In this work, we combine a graph-based approach with homology modeling to expand the library of conotoxin structures and to identify those conotoxin sequences that are of the greatest value for experimental structural characterization. The latter would allow for the rapid expansion of the known structural space for generating high quality template-based models. Our approach generalizes to other evolutionarily-related, short, cysteine-rich venoms of interest. Overall, we present and validate an approach for venom structure modeling and experimental guidance and employ it to produce a 290%-larger library of approximate conotoxin structures for HTS. We also provide a set of ranked conotoxin sequences for experimental structure determination to further expand this library.

APA, Harvard, Vancouver, ISO, and other styles

36

Lin, Ting-Yen, and Ching-Liang Hsieh. "Clinical Applications of Bee Venom Acupoint Injection." Toxins 12, no. 10 (September 27, 2020): 618. http://dx.doi.org/10.3390/toxins12100618.

Full text

Abstract:

Bee venom is a complex natural mixture with various pharmaceutical properties. Among these properties, its peptides and enzymes have potential medical therapy for pain relief and inflammation. In clinical settings, this therapy has been used widely to treat diseases by injecting into acupoints. In this article, we have conducted various research from PubMed, Cochrane Library, and Clinical Key from inception of July 2020. The results revealed that bee venom therapy has been reported effective in anti-inflammatory, antiapoptosis, and analgesic effects. Moreover, bee venom acupuncture has been commonly used for clinical disorders such as Parkinson disease, neuropathic pain, Alzheimer disease, intervertebral disc disease, spinal cord injury, musculoskeletal pain, arthritis, multiple sclerosis, skin disease and cancer.

APA, Harvard, Vancouver, ISO, and other styles

37

Kuzmenkov, Alexey I., Maria Y. Sachkova, Sergey I. Kovalchuk, Eugene V. Grishin, and Alexander A. Vassilevski. "Lachesana tarabaevi, an expert in membrane-active toxins." Biochemical Journal 473, no. 16 (August 11, 2016): 2495–506. http://dx.doi.org/10.1042/bcj20160436.

Full text

Abstract:

In the present study, we show that venom of the ant spider Lachesana tarabaevi is unique in terms of molecular composition and toxicity. Whereas venom of most spiders studied is rich in disulfide-containing neurotoxic peptides, L. tarabaevi relies on the production of linear (no disulfide bridges) cytolytic polypeptides. We performed full-scale peptidomic examination of L. tarabaevi venom supported by cDNA library analysis. As a result, we identified several dozen components, and a majority (∼80% of total venom protein) exhibited membrane-active properties. In total, 33 membrane-interacting polypeptides (length of 18–79 amino acid residues) comprise five major groups: repetitive polypeptide elements (Rpe), latarcins (Ltc), met-lysines (MLys), cyto-insectotoxins (CIT) and latartoxins (LtTx). Rpe are short (18 residues) amphiphilic molecules that are encoded by the same genes as antimicrobial peptides Ltc 4a and 4b. Isolation of Rpe confirms the validity of the iPQM (inverted processing quadruplet motif) proposed to mark the cleavage sites in spider toxin precursors that are processed into several mature chains. MLys (51 residues) present ‘idealized’ amphiphilicity when modelled in a helical wheel projection with sharply demarcated sectors of hydrophobic, cationic and anionic residues. Four families of CIT (61–79 residues) are the primary weapon of the spider, accounting for its venom toxicity. Toxins from the CIT 1 and 2 families have a modular structure consisting of two shorter Ltc-like peptides. We demonstrate that in CIT 1a, these two parts act in synergy when they are covalently linked. This finding supports the assumption that CIT have evolved through the joining of two shorter membrane-active peptides into one larger molecule.

APA, Harvard, Vancouver, ISO, and other styles

38

Tang, Xing, Jing Yang, Zhigui Duan, Liping Jiang, Zhonghua Liu, and Songping Liang. "Molecular diversification of antimicrobial peptides from the wolf spider Lycosa sinensis venom based on peptidomic, transcriptomic, and bioinformatic analyses." Acta Biochimica et Biophysica Sinica 52, no. 11 (October 22, 2020): 1274–80. http://dx.doi.org/10.1093/abbs/gmaa107.

Full text

Abstract:

Abstract The venom of Lycosoidea spiders is a complex multicomponent mixture of neurotoxic peptides (main components) and antimicrobial peptides (AMPs) as minor components. In this study, we described the high-throughput identification and analysis of AMPs from Lycosa sinensis venom (named LS-AMPs) using a combination strategy that includes the following three different analysis approaches: (i) peptidomic analysis, namely reversed-phase high-performance liquid chromatography (RP-HPLC) separation plus top-down sequencing by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS); (ii) transcriptomic analysis, namely cDNA library construction plus DNA sequencing; (iii) bioinformatic analysis, namely analysis and prediction for molecular characters of LS-AMPs by the online biology databases. In total, 52 sequences of AMPs were identified from L. sinensis venom, and all AMPs can be categorized into eight different families according to phylogenetic analysis and sequence identity. This is the largest number of AMPs identified from a spider species so far. In the present study, we demonstrated molecular characteristics, such as complex precursor, N- and/or C-terminally truncated analogs, and C-terminal amidation of LS-AMPs from L. sinensis venom. This is a preliminary investigation on the molecular diversification of venom-derived AMPs from the wolf spider species (family Lycosidae), and a detailed investigation on the functional diversity of LS-AMPs will be preformed in the future.

APA, Harvard, Vancouver, ISO, and other styles

39

Van Baelen, Anne-Cécile, Xavier Iturrioz, Marion Chaigneau, Pascal Kessler, Catherine Llorens-Cortes, Denis Servent, Nicolas Gilles, and Philippe Robin. "Characterization of the First Animal Toxin Acting as an Antagonist on AT1 Receptor." International Journal of Molecular Sciences 24, no. 3 (January 24, 2023): 2330. http://dx.doi.org/10.3390/ijms24032330.

Full text

Abstract:

The renin-angiotensin system (RAS) is one of the main regulatory systems of cardiovascular homeostasis. It is mainly composed of angiotensin-converting enzyme (ACE) and angiotensin II receptors AT1 and AT2. ACE and AT1 are targets of choice for the treatment of hypertension, whereas the AT2 receptor is still not exploited due to the lack of knowledge of its physiological properties. Peptide toxins from venoms display multiple biological functions associated with varied chemical and structural properties. If Brazilian viper toxins have been described to inhibit ACE, no animal toxin is known to act on AT1/AT2 receptors. We screened a library of toxins on angiotensin II receptors with a radioligand competition binding assay. Functional characterization of the selected toxin was conducted by measuring second messenger production, G-protein activation and β-arrestin 2 recruitment using bioluminescence resonance energy transfer (BRET) based biosensors. We identified one original toxin, A-CTX-cMila, which is a 7-residues cyclic peptide from Conus miliaris with no homology sequence with known angiotensin peptides nor identified toxins, displaying a 100-fold selectivity for AT1 over AT2. This toxin shows a competitive antagonism mode of action on AT1, blocking Gαq, Gαi3, GαoA, β-arrestin 2 pathways and ERK1/2 activation. These results describe the first animal toxin active on angiotensin II receptors.

APA, Harvard, Vancouver, ISO, and other styles

40

Luan, Ning, Qiyu Zhao, Zilei Duan, Mengyao Ji, Meichen Xing, Tengyu Zhu, James Mwangi, Mingqiang Rong, Jiangxin Liu, and Ren Lai. "Identification and Characterization of ShSPI, a Kazal-Type Elastase Inhibitor from the Venom of Scolopendra Hainanum." Toxins 11, no. 12 (December 5, 2019): 708. http://dx.doi.org/10.3390/toxins11120708.

Full text

Abstract:

Elastase is a globular glycoprotein and belongs to the chymotrypsin family. It is involved in several inflammatory cascades on the basis of cleaving the important connective tissue protein elastin, and is strictly regulated to a balance by several endogenous inhibitors. When elastase and its inhibitors are out of balance, severe diseases will develop, especially those involved in the cardiopulmonary system. Much attention has been attracted in seeking innovative elastase inhibitors and various advancements have been taken on clinical trials of these inhibitors. Natural functional peptides from venomous animals have been shown to have anti-protease properties. Here, we identified a kazal-type serine protease inhibitor named ShSPI from the cDNA library of the venom glands of Scolopendra hainanum. ShSPI showed significant inhibitory effects on porcine pancreatic elastase and human neutrophils elastase with Ki values of 225.83 ± 20 nM and 12.61 ± 2 nM, respectively. Together, our results suggest that ShSPI may be an excellent candidate to develop a drug for cardiopulmonary diseases.

APA, Harvard, Vancouver, ISO, and other styles

41

Satake, H., E. Villegas, N. Oshiro, K. Terada, T. Shinada, and G. Corzo. "Rapid and efficient identification of cysteine-rich peptides by random screening of a venom gland cDNA library from the hexathelid spider Macrothele gigas." Toxicon 44, no. 2 (August 2004): 149–56. http://dx.doi.org/10.1016/j.toxicon.2004.05.012.

Full text

APA, Harvard, Vancouver, ISO, and other styles

42

Takasaki, C., S. Kimura, Y. Kokubun, and N. Tamiya. "Isolation, properties and amino acid sequences of a phospholipase A2 and its homologue without activity from the venom of a sea snake, Laticauda colubrina, from the Solomon Islands." Biochemical Journal 253, no. 3 (August 1, 1988): 869–75. http://dx.doi.org/10.1042/bj2530869.

Full text

Abstract:

A phospholipase A2, Laticauda colubrina phospholipase A2 II (LcPLA-II), and a phospholipase A2 homologue, Laticauda colubrina phospholipase A2 homologue I (LcPLH-I), were isolated from the venom of the yellow-lipped sea snake, Laticauda colubrina, from the Solomon Islands. LcPLA-II showed phospholipase A2 activity towards egg-yolk phosphatidylcholine (24 mumol/min per mg at optimal conditions at 37 degrees C) and lethal potency (LD50 45 micrograms/kg body wt. intravenously in mice). Both of the activities were lost by treatment with p-bromophenacyl bromide. LcPLH-I showed neither phospholipase A2 activity nor lethal potency at a dose of 4.5 mg/kg body wt. in mice. It was not modified by the treatment with p-bromophenacyl bromide. LcPLA-II and LcPLH-I bound Ca2+ at a 1:1 molar ratio with KCa values of 105 microM and 44 microM at pH 8.0 respectively. Elucidation of the amino acid sequences of these two proteins showed that each protein consisted of a single chain of 118 amino acid residues, including 14 half-cystine residues. The two sequences are different from each other at 22 residues and highly homologous to those from other sources. The essential histidine residue for the phospholipase A2 activity at position 48 is replaced by an asparagine residue in the homologue LcPLH-I. Details of the separation of the peptides obtained by proteinase digestions of LcPLA-II and LcPLA-I and the determination of their amino acid sequences are given in Supplementary Publication SUP 50145 (14 pages), which has been deposited at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1988) 249, 5.

APA, Harvard, Vancouver, ISO, and other styles

43

Jalali, Amir, Masoud Mahdavinia, Hamid Galehdari, Masoumeh Baradaran, Davood Valdi-Biranvand, and Maryam Naderi Soork. "Molecular Characterization of a cDNA Encoding of an Anionic Cysteine-Free Antimicrobial Peptide From the Iranian Scorpion Odontobuthus Doriae Venom Glands." Pharmaceutical and Biomedical Research, October 30, 2022. http://dx.doi.org/10.18502/pbr.v8i3.11034.

Full text

Abstract:

Background: The venom peptides from the scorpion fauna of Iran have been poorly characterized so far. Objectives: In this study, we identified a cDNA encoding of an anionic cysteine-free antimicrobial peptide from the Iranian yellow scorpion odontobuthus doriae (O.doriae). Methods: The cDNA sequence of an anionic antimicrobial-peptide (AMP) was determined from the venom gland cDNA library of Iranian yellow scorpion O.doriae and was named ODAMP5. This sequence was characterized by a software. Then, the structure and function of its putative peptide were predicted in a bioinformatics manner. The library was constructed from 6 scorpion venom glands. The cDNA related to ODAMP5 was isolated from one positive clone of the library. Results: The analysis of ODAMP5 reveals a 51-residue mature peptide with an anionic property that was stable in physiological states. ODAMP5 was similar to anionic peptide Aba-2 from Androctonus bicolor and according to its structure, it can be a member of helical structure AMPs with a new type of putative conserved domain. Putative ODAMP5 has a small size which makes it convenient for synthesis. Conclusion: Furthermore, we created a framework to express the ODAMP5 peptide for future biomedical and pharmacological studies. ODAMP5 may be a new suitable therapeutic strategy for bacterial infection among a few recognized scorpion venom peptides without disulfide bridges.

APA, Harvard, Vancouver, ISO, and other styles

44

Liao, Yanling, Chao Peng, Yabing Zhu, Jinxing Fu, Zhiqiang Ruan, Qiong Shi, and Bingmiao Gao. "High conopeptide diversity in Conus striatus: Revealed by integration of two transcriptome sequencing platforms." Frontiers in Marine Science 9 (November 15, 2022). http://dx.doi.org/10.3389/fmars.2022.1060432.

Full text

Abstract:

Marine cone snail venoms represent a vast library of bioactive peptides with proven potential as research tools, drug leads, and therapeutics. In this study, a transcriptome library of four different organs, namely radular sheath, venom duct, venom gland, and salivary gland, from piscivorous Conus striatus was constructed and sequenced using both Illumina next-generation sequencing (NGS) and PacBio third-generation sequencing (TGS) technologies. A total of 428 conotoxin precursor peptides were retrieved from these transcriptome data, of which 413 conotoxin sequences assigned to 13 gene superfamilies, and 15 conotoxin sequences were classified as unassigned families. It is worth noting that there were significant differences in the diversity of conotoxins identified from the NGS and TGS data: 82 conotoxins were identified from the NGS datasets while 366 conotoxins from the TGS datasets. Interestingly, we found point mutations in the signal peptide sequences of some conotoxins with the same mature sequence. Therefore, TGS broke the traditional view of the conservation of conotoxin signal peptides and the variability of mature peptides obtained by NGS technology. These results shed light on the integrated NGS and TGS technologies to mine diverse conotoxins in Conus species, which will greatly contribute to the discovery of novel conotoxins and the development of new marine drugs.

APA, Harvard, Vancouver, ISO, and other styles

45

de Moura, Gabriel A., Juliana R. de Oliveira, Yasmim M. Rocha, Janaína de Oliveira Freitas, João Pedro V. Rodrigues, Vanessa P. G. Ferreira, and Roberto Nicolete. "Antitumor and antiparasitic activity of antimicrobial peptides derived from snake venom: a systematic review approach." Current Medicinal Chemistry 29 (May 7, 2022). http://dx.doi.org/10.2174/0929867329666220507011719.

Full text

Abstract:

Background: In a scenario of increased pathogens with multidrug resistance phenotypes, it is necessary to seek new pharmacological options. This fact is responsible for an increase in neoplasms and multiresistant parasitic diseases. In turn, snake venom-derived peptides exhibited cytotoxic action on fungal and bacterial strains, possibly presenting activities in resistant tumor cells and parasites. Therefore, the aim of this work is to verify an antitumor and antiparasitic activity of antimicrobial peptides derived from snake venom. Methods: For this purpose, searches were performed in the Pubmed, Embase and Virtual Health Library databases by combining the descriptors peptides, venom and snake with antitumor/ antiparasitic agent and in silico. The inclusion criteria: in vitro and in vivo experimental articles in addition to in silico studies. The exclusion criteria: articles that were out of scope, review articles, abstracts, and letters to the reader. Data extracted: peptide name, peptide sequence, semi-maximal inhibitory concentration, snake species, tumor lineage or parasitic strain, cytotoxicity, in vitro and in vivo activity. Results: In total 164 articles were found, of which 14 were used. A total of ten peptides with antiproliferative activity on tumor cells were identified. Among the articles, seven peptides addressed the antiparasitic activity. Conclusion: In conclusion, snake venom-derived peptides can be considered as potential pharmacological options for parasites and tumors, however more studies are needed to prove their specific activity.

APA, Harvard, Vancouver, ISO, and other styles

46

Chai, Lin, Xianyi Yang, Mei Liu, Chunyan Liu, Limei Han, Hui Guo, Changsheng Li, et al. "Biopanning of allergens from wasp sting patients." Bioscience Reports 38, no. 5 (October 17, 2018). http://dx.doi.org/10.1042/bsr20181113.

Full text

Abstract:

Objective: Wasp venom is a potentially important natural drug, but it can cause hypersensitivity reactions. The purpose of the present study was to systematically study the epitopes of wasp venom. Methods: Using a random 12-peptide phage library, we performed antibody-binding epitope panning on ten serum samples from wasp sting victims at 3 h and 4 days after the sting. The panning epitopes were identified by high-throughput sequencing and matched with wasp venom proteins by BLAST. The panned antibody-binding epitopes were verified by ELISA. Results: A total of 35 specific potential wasp venom epitopes in 4 days were identified. Amongst them, twelve peptide epitopes were matched with nine wasp venom proteins, namely, vitellogenin precursor, hexamerin 70b precursor, venom carboxylesterase-6 precursor, MRJP5, major royal jelly protein 8 precursor, venom acid phosphatase Acph-1 precursor, phospholipase A2, venom serine protease 34 precursor, and major royal jelly protein 9 precursor. The changes in serum IgM antibodies induced by wasp venom were confirmed by ELISA based on the 12 peptide epitopes. Conclusion: The nine wasp venom proteins are potential allergens, which should be excluded or modified in the potential biomedical applications of wasp venom.

APA, Harvard, Vancouver, ISO, and other styles

47

Galante, Priscilla, Gabriel A. A. Campos, Jacqueline C. G. Moser, Danubia B. Martins, Marcia P. dos Santos Cabrera, Marisa Rangel, Luiza C. Coelho, et al. "Exploring the therapeutic potential of an antinociceptive and anti-inflammatory peptide from wasp venom." Scientific Reports 13, no. 1 (August 1, 2023). http://dx.doi.org/10.1038/s41598-023-38828-w.

Full text

Abstract:

AbstractAnimal venoms are rich sources of neuroactive compounds, including anti-inflammatory, antiepileptic, and antinociceptive molecules. Our study identified a protonectin peptide from the wasp Parachartergus fraternus' venom using mass spectrometry and cDNA library construction. Using this peptide as a template, we designed a new peptide, protonectin-F, which exhibited higher antinociceptive activity and less motor impairment compared to protonectin. In drug interaction experiments with naloxone and AM251, Protonectin-F's activity was decreased by opioid and cannabinoid antagonism, two critical antinociception pathways. Further experiments revealed that this effect is most likely not induced by direct action on receptors but by activation of the descending pain control pathway. We noted that protonectin-F induced less tolerance in mice after repeated administration than morphine. Protonectin-F was also able to decrease TNF-α production in vitro and modulate the inflammatory response, which can further contribute to its antinociceptive activity. These findings suggest that protonectin-F may be a potential molecule for developing drugs to treat pain disorders with fewer adverse effects. Our results reinforce the biotechnological importance of animal venom for developing new molecules of clinical interest.

APA, Harvard, Vancouver, ISO, and other styles

48

Chase, Kevin, Maren Watkins, Helena Safavi-Hemami, and Baldomero M. Olivera. "Integrating Venom Peptide Libraries Into a Phylogenetic and Broader Biological Framework." Frontiers in Molecular Biosciences 9 (February 21, 2022). http://dx.doi.org/10.3389/fmolb.2022.784419.

Full text

Abstract:

The venomous marine snails are conventionally divided into three groups, the cone snails (family Conidae), the auger snails (family Terebridae) and the turrids (formerly all assigned to a single family, Turridae). In this study, a library of venom peptides from species conventionally assigned to the genus Turris was correlated to a phylogenetic analysis. Nucleotide sequences of multiple genes from transcriptomes were used to assess the phylogenetic relationships across a diverse set of species. The resulting tree shows that as conventionally defined, the conoidean genus Turris, is polyphyletic. We describe a new genus, Purpuraturris gen. nov., that comprises the outlier species. In addition to morphological distinctions, molecular data reveal that this group is divergent from Turris sensu stricto. The correlation between phylogenetic information and a family of peptide sequences was used to highlight those peptides mostly likely to be unique and intimately associated with biological diversity. The plethora of peptide sequences available requires two prioritization decisions: which subset of peptides to initially characterize, and after these are characterized, which to comprehensively investigate for potential biomedical applications such as drug developments.Life Science Identifiers: urn:lsid:zoobank.org; pub: 60D46561-28F0-4C39-BAC4-66DC8B4EAEA4

APA, Harvard, Vancouver, ISO, and other styles

49

Zhang, Yubiao, Feng Zhang, Shujuan Shi, Xinqiao Liu, Weisong Cai, Guangtao Han, Caihua Ke, et al. "Immunosuppressive effects of a novel potassium channel toxin Ktx-Sp2 from Scorpiops Pocoki." Cell & Bioscience 9, no. 1 (December 2019). http://dx.doi.org/10.1186/s13578-019-0364-1.

Full text

Abstract:

Abstract Background The cDNA Library of venomous animals could provide abundant bioactive peptides coding information and is an important resource for screening bioactive peptides that target and regulate disease-related ion channels. To further explore the potential medicinal usage of the transcriptome database of Scorpiops Pocoki’s venom gland, this research identified the function of a new potassium channel toxin Ktx-Sp2, whose gene was screened from the database by sequence alignment. Results The mature peptide of Ktx-Sp2 was obtained by genetic engineering. Whole-cell patch-clamp experiment showed that Ktx-Sp2 peptide could effectively block three types of exogenous voltage-gated potassium channels—Kv1.1, Kv1.2 and Kv1.3, among which, the blocking activity for Kv1.3 was relatively high, showing selectivity to some extent. Taking Jurkat T cells as the cell model, this study found that Ktx-Sp2 peptide could also effectively block endogenous Kv1.3, significantly reduce the free calcium concentration in Jurkat T cells, inhibit the activation of Jurkat T cells and reduce the release of inflammatory cytokines IL-2, showing a strong immunosuppressant effect. Conclusions This study further proves that the transcriptome database of the Scorpiops Pocoki venom gland is an important resource for discovery of novel bioactive polypeptide coding genes. The newly screened Kv1.3 channel blocker Ktx-Sp2 expanded the range of leading compounds for the treatment of autoimmune diseases and promoted the development and application of scorpion toxin peptides in the field of biomedicine.

APA, Harvard, Vancouver, ISO, and other styles

50

Nie, Xuekui, Qiyi He, Bin Zhou, Dachun Huang, Junbo Chen, Qianzi Chen, Shuqing Yang, and Xiaodong Yu. "Exploring the five-paced viper (Deinagkistrodon acutus) venom proteome by integrating a combinatorial peptide ligand library approach with shotgun LC-MS/MS." Journal of Venomous Animals and Toxins including Tropical Diseases 27 (2021). http://dx.doi.org/10.1590/1678-9199-jvatitd-2020-0196.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Venom Peptide Library'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles