Academic literature on the topic 'Bi-peptide'

Fe3O4 magnetic nanoparticles (Fe3O4-MNPs) have attracted much interest for their potential medical applications due to their desirable magnetic properties. However, their potential cytotoxicity, high RES clearance in circulation, and nonspecific distribution in tissue might be the main obstacles in practice. In the present study, a novel bi-functional 14-mer peptide with both ovarian carcinoma cells targeting and magnetic Fe3O4 nanoparticles affinity was designed and synthesized, and then a facile and effective modification method was developed to bestow the Fe3O4-MNPs with tumor-targeting capability via modification, using the bi-functional peptides. First, on the basis of a tumor-targeting 7-mer peptide QQTNWSL (Q-L) and another Fe3O4-MNPs-targeting 7-mer peptide TVNFKLY (T-Y)—screened by phage-displayed peptide libraries—two bi-functional 14-mer peptides sequenced as LSWNTQQ-YLKFNVT (abbreviated as LQ-YT) and QQTNWSL-YLKFNVT (QL-YT) were synthesized through combining the Q-L peptide and T-Y peptide in predetermined configurations. Their specificity for bonding with A2780 tumor cells and affinity for Fe3O4-MNPs were verified. Then the bi-functional 14-mer peptides were applied to modify the Fe3O4-MNPs. Results showed that both bi-functional 14-mer peptides could be conjugated to the Fe3O4-MNPs surface with high affinity. Immunofluorescence and Prussian blue staining assays indicated that the LQ-YT-modified Fe3O4-MNPs could specifically bond to A2780 tumor cells. In addition to our findings suggesting that more β-turns and random coils are conducive to increasing polypeptide surface area for binding and exposing the target group and bonding sites on LQ-YT to external targets, we demonstrated that the bi-functional 14-mer peptide has affinity for Fe3O4-MNPs, and that Fe3O4-MNPs, which was modified with a 14-mer peptide, could be bestowed with a targeting affinity for ovarian carcinoma cells.

The first total synthesis of natural lasso peptide is reported, in which cryptand-imidazolium complex support manipulates the peptide chain to achieve a lasso peptide configuration of BI-32169. Moreover, the synthesis of d-enantiomeric lasso peptide via this new method opens up new horizons in the study of lasso peptides.

Everolimus inhibits stent restenosis and the WKYMV (fluorescein isothiocyanate) peptide promotes endothelial homing. Dextran is a natural polymer that is widely used as a pharmaceutical agent. The purpose of this study was to develop a double-drug-coated stent using a bidirectional coating system and to examine the surface shape with in vitro experiments. Stent length was 16 mm and strut thickness was 70 µm (Chonnam National University Hospital Tiger stent). Optical and scanning electron microscopy showed good coating without cracks or bubbles. Fluorescein isothiocyanate-peptide was dip-coated on the lumen and the abluminal surface was coated with everolimus and dextran. Stents were coated with dextran, everolimus, or everolimus–dextran. The radial force and flexibility were measured to determine the mechanical properties. Contact angle testing was performed in all groups. Dextran and peptide as hydrophilic substances and everolimus as a hydrophobic substance were each coated on cover glasses (cobalt–chromium). A10 and human umbilical vein endothelial cells were used in the experiments. Water and dimethyl sulfoxide served as a control, and three drug groups were tested: peptide–everolimus, everolimus–dextran, and peptide–everolimus–dextran. Immunocytochemistry was performed to assess cell adhesion. Light intensity was plotted according to the average on nuclear staining. Experiments were conducted using 5-bromo-2′-deoxyuridine to investigate A10 and human umbilical vein endothelial cell proliferation. Cell adhesion and proliferation of peptide–everolimus–dextran were inhibited at A10, and human umbilical vein endothelial cell was found to proliferate with cell adhesion. On conclusion, dextran and peptide–everolimus bidirectional stent is effective in re-endothelialization and inhibition of cell proliferation.

Polymer substrates were modified with hydroxyapatite (HAp) using two bi-functional peptides consists of polymer-binding peptide and triasparate for HAp mineralization in simulated body fluids and HAp-binding peptide for immobilization HAp nanoparticles.

ABSTRACT Bax inhibitor 1 (BI-1), a transmembrane protein with Ca2+ channel-like activity, has antiapoptotic and anticancer activities. Cells overexpressing BI-1 demonstrated increased cell adhesion. Using a proteomics tool, we found that BI-1 interacted with γ-actin via leucines 221 and 225 and could control actin polymerization and cell adhesion. Among BI-1−/− cells and cells transfected with BI-1 small interfering RNA (siRNA), levels of actin polymerization and cell adhesion were lower than those among BI-1+/+ cells and cells transfected with nonspecific siRNA. BI-1 acts as a leaky Ca2+ channel, but mutations of the actin binding sites (L221A, L225A, and L221A/L225A) did not change intra-endoplasmic reticulum Ca2+, although deleting the C-terminal motif (EKDKKKEKK) did. However, store-operated Ca2+ entry (SOCE) is activated in cells expressing BI-1 but not in cells expressing actin binding site mutants, even those with the intact C-terminal motif. Consistently, actin polymerization and cell adhesion were inhibited among all the mutant cells. Compared to BI-1+/+ cells, BI-1−/− cells inhibited SOCE, actin polymerization, and cell adhesion. Endogenous BI-1 knockdown cells showed a similar pattern. The C-terminal peptide of BI-1 (LMMLILAMNRKDKKKEKK) polymerized actin even after the deletion of four or six charged C-terminal residues. This indicates that the actin binding site containing L221 to D231 of BI-1 is responsible for actin interaction and that the C-terminal motif has only a supporting role. The intact C-terminal peptide also bundled actin and increased cell adhesion. The results of experiments with whole recombinant BI-1 reconstituted in membranes also coincide well with the results obtained with peptides. In summary, BI-1 increased actin polymerization and cell adhesion through Ca2+ regulation and actin interaction.

Cardiovascular disease states including hypertension and vascular stiffness are precursors of cardiac damage such as heart failure. The prevalence of cardiovascular disease among the African population in South Africa is also increasing dramatically. The N–terminal prohormone B–type natriuretic peptide (NT–proBNP) is a reliable biomarker and predictor of cardiovascular risk and heart failure. During the onset and development of heart failure, the heart undergoes structural and functional changes including hypertrophy and vascular remodelling. NT–proBNP levels are normally lower in men compared to women, but less is known about ethnic differences and also the associations between NT–proBNP and measures of cardiovascular function. Information on factors affecting vascular function and therefore the synergy between blood vessels and the heart leading to cardiac damage in a bi–ethnic South African population is also scant. Therefore, this study included markers of both atherosclerosis (C–reactive protein, soluble urokinase plasminogen activator receptor, fibulin–1) and arteriosclerosis (arterial compliance and alkaline phosphatase) to address the underlying vascular changes that augment cardiac load and damage. The lack of information in this regard, especially in South Africans, serves as motivation for this study. Aim The purpose of this study was to explore the possible associations of NT–proBNP with cardiovascular function and also biochemical components that may contribute to the development of cardiovascular disease in both African and Caucasian men and women. Methodology Data from the South African study regarding the role of Sex, Age and Ethnicity on Insulin sensitivity and Cardiovascular function (SAfrEIC) were used, and presented in the manuscript Chapters 3, 4, 5 and 6. This study included 756 Africans and Caucasians in total. Groups were stratified by ethnicity or gender, or both ethnicity and gender as specified by statistical interaction terms. Cardiovascular measurements were performed and NT–proBNP, fibulin–1, high sensitivity Creactive protein (CRP), soluble urokinase plasminogen activator receptor (suPAR) and also alkaline phosphatase (ALP) levels were determined. Means were compared with either T–tests or analysis of variance (ANOVA). Significant differences between groups were also tested with analysis of covariance (ANCOVA) with adjustments applied for age, body mass index (BMI) and systolic blood pressure (SBP). Partial correlations were performed to investigate associations between various variables with adjustments applied for age, BMI and SBP. Multiple regression analyses were performed to investigate independent associations between variables in the different groups. Results and conclusions of each manuscript The first paper in this thesis (Chapter 3) aimed to compare NT–proBNP as a marker of cardiac load and its possible associations with markers of cardiovascular function in Africans and Caucasians. The results indicated that the African population revealed higher NT–proBNP levels compared to Caucasians, however, these were partially confounded by SBP and completely by arterial compliance. NT–proBNP was positively associated with both SBP and pulse pressure in Africans, but not in Caucasians. Also, after adjustments were applied for significant covariates and confounders, the positive significant association remained in Africans only. These associations may suggest early vascular changes contributing to cardiac alterations in Africans. The aim in Chapter 4 was to explore the relationship between NT–proBNP and fibulin–1 (an extracellular matrix component and also expressed in atherosclerotic lesions) in African and Caucasian men and women. NT–proBNP was positively associated with fibulin–1 in African men only after adjustments were applied for age, BMI, SBP, heart rate and estimated creatinine clearance. No significant link existed between NT–proBNP and measures of arterial stiffness in any of the groups. However, after full adjustment, the positive significant association between NT–proBNP and fibulin–1 was confirmed in African men and also in younger African men and women after excluding participants older than 55 years. These associations were not present in the Caucasians. This suggests that vascular alterations also occur in young African men and women and that they may be prone to develop cardiovascular disease much earlier as opposed to Caucasian men and women. Due to earlier vascular changes present in the African population, we aimed to investigate the link between NT–proBNP and inflammatory markers (both CRP and suPAR) in African men and women (Chapter 5), independent of a hypertensive state. Although the levels of NT–proBNP and inflammatory markers were lower in men compared to women, the results showed that NTproBNP is positively and significantly associated with both CRP and suPAR in the normotensive African men only. No significant association was observed in normotensive African women. After full adjustments in multiple regression analyses, the positive significant association between NT–proBNP, CRP and suPAR was confirmed in African men. This suggests that in a low–grade inflammatory state, normotensive African men are more susceptible to developing vascular alterations that may result in cardiac overload and damage. In Chapter 6 we explored the possible association of NT–proBNP with a marker of osteoblastactivity, alkaline phosphatase (ALP). This sub–study was performed in a bi–ethnic male population. The results revealed a positive association between NT–proBNP and ALP in African men, but not in Caucasian men. African men also had higher NT–proBNP and ALP levels as opposed to Caucasian men. After adjusting for significant covariates, the link between cardiac strain and osteoblastic activity, and possible vascular calcification was confirmed in African men. This population seems to have a higher susceptibility to develop sclerosis in either the media or intima, which could contribute to cardiovascular damage due to a possible increased cardiac afterload. General conclusion NT–proBNP, a reliable marker of cardiac overload and damage, was positively associated with systolic blood pressure, pulse pressure, fibulin–1, C–reactive protein, soluble urokinase plasminogen activator receptor and alkaline phosphatase. Throughout this study, our findings were persistent in the black South African population, especially African men. These results indicate that the earlier burden of cardiovascular disease in young Africans may result from early vascular changes due to inflammation, extracellular matrix alterations and calcification which could cascade into cardiac strain and damage.
Thesis (PhD (Physiology))--North-West University, Potchefstroom Campus, 2012.

Chez les eucaryotes, la plupart des protéines sont transférées aux organelles par de nombreux signaux d'adressage. Les plastes, acquis par endosymbiose secondaire, possèdent des structures très complexes avec plus de deux membranes. Nous avons développé la méthode HECTAR qui prend en considération l'adressage complexe au plaste des hétérokontes par une approche hiérarchique avec plusieurs modules. Dans chaque module des méthodes de prédiction dédiées à la détection d'un signal d'adressage spécifique sont combinées par une machine à vecteur support. La localisation subcellulaire a été analysée pour des génomes des 37 organismes de quatre groupes d’eucaryotes. Les espèces multicellulaires chez les plantes et les champignons semblent avoir une plus grande quantité de protéines de chemin de sécrétion que les organismes unicellulaires dans les groupes correspondants. La proportion de protéines secrétées chez les métazoaires est la plus haute

>Magister Scientiae - MSc
The therapeutic goal of cancer treatment is to trigger selective cell death in cancer cells. To eliminate cancerous cells effectively, the anti–cancer drugs must be targeted to the affected cells. However, anti–cancer drugs are often distributed non–specifically giving rise to systemic toxicities and other adverse effects. Cancer specific peptides are useful cancer targeting agents that can be used for the targeted delivery of anti-cancer drugs. Several cancer targeting peptides and some of their corresponding protein targets have been identified. Previous work investigated the specific binding of five of these peptides (p.C, p.H, p6.1, Frop-1 and p.L) conjugated to fluorescent nanoparticles (quantum dots) to a panel of human cell lines, which included four cancerous cell lines (Caco-2, HeLa, HT29 and HepG2) and one non-cancerous cell line (KMST-6). Flow cytometry showed that the p.L peptide preferentially bind to HT29 cells; suggesting that the expression levels of the target for the p.L peptide are higher in these cells. The objective of this study was to make use of target specific functionalised quantum dots (QDs) to deliver Second mitochondria-derived activator of caspases/ Direct AIP binding protein with low PI (Smac/DIABLO) to HT29 cells with the aim of enhancing the effects of pro-apoptotic drugs. Smac/DIABLO is a pro-apoptotic peptide that is able to interact with inhibitor of apoptosis proteins (IAPs), thereby inducing pro-apoptotic signalling. Methodology: CdSe/ZnS core-shell QDs were synthesised using the one-pot synthesis method. These QDs were characterised using photoluminescence (PL) spectroscopy, high resolution transmission electron microscopy (HR-TEM) and energy dispersive x-ray spectroscopy (EDS). The CdSe/ZnS core-shell QDs were solubilised with L-cysteine (Cys- QDs). The Cys-QDs were bi-conjugated to the p.L peptide and Smac peptide using 1-ethyl-3- (30-dimethylamino) carbodiimide (EDC) chemistry. Cultured HT29 cells were exposed to the 10 | P a g e QD peptide bi-conjugates and fluorescence microscopy was employed to assess targeting and internalisation. The cytotoxicity of the QD peptide bi-conjugates in combinatorial treatment with ceramide was evaluated using the WST-1 Cell Proliferation assay. A commercially available QD with similar chemistry was used to carry out a comparative study to relate the efficiency of the in-house synthesized QD.