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Dissertations / Theses on the topic 'Beta lactam antibiotics – Synthesis'

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Published: 4 June 2021
Last updated: 13 February 2022

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1

Hadfield, Peter Stanley. "The synthesis of #gamma#-lactam mimics of #beta#-lactam antibiotics." Thesis, University of Huddersfield, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338614.

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2

Schofield, C. "Chemical and enzymatic synthesis of beta-lactam antibiotics." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355775.

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3

Freeman, Richard Neil Templar. "The total synthesis of non-beta-lactam antibiotics." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.257963.

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4

Knight, J. "New synthetic methods for the synthesis of #BETA#-lactam antibiotics." Thesis, University of Southampton, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373921.

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5

Cox, G. "Synthesis of carbocyclic analogues of the #beta#-lactam antibiotics." Thesis, University of Huddersfield, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374894.

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6

Sakhnini, Nina Issam. "The synthesis of novel compounds related to #beta#-lactam antibiotics." Thesis, University of Sussex, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359204.

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7

Goh, Kee Chuan. "The biosynthesis of β-lactams." Thesis, University of Oxford, 1993. http://ora.ox.ac.uk/objects/uuid:24b6b29d-87cc-48f2-bd1b-bb64c663604f.

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This thesis reports the work done on two research projects which were carried out independently of each other but converge on the central theme of β-lactam biosynthesis. Chapter 1 provides an overview of biosynthesis in secondary metabolism, with special emphasis on current knowledge about the β-lactams. The first project, covered from Chapters 2 to 5, was part of our group's continuing effort to understand the structure and mechanism of Ring Expandase-Hydroxylase (REXH), an enzyme involved in the biosynthesis of cephalosporin C in Cephalosporium acremonium. REXH is a bifunctional enzyme, converting penicillin N to DAOC and thence to DAC. [diagram omitted from transcription] Chapter 3 discusses the investigation of purification protocols for native REXH and soluble recombinant REXH, as well as an improved refolding method for recombinant REXH expressed as inclusion bodies. Chapter 4 describes two new alternative substrates for REXH, viz. carba-DAOC and DAC, whilst the y-lactam analogue of penicillin N was not found to be a substrate for REXH. Chapter 5 summarises some structural investigations of REXH employing methods such as electrospray mass spectrometry, selective proteolysis and inhibition kinetics. [diagram omitted from transcription] The second project, covered from Chapters 6 to 9, represents the first biosynthetic studies on valclavam, an antifungal produced by Streptomyces antibioticus. Valclavam belongs to the family of clavams which includes clavulanic acid as its most well studied member. [diagram omitted from transcription] Chapter 7 details the development of methods for the bioassay, fermentation and isolation of valclavam. It also describes the isolation of a stable degradation fragment of valclavam which led to the revision of the structures of valclavam and Tü 1718B (another metabolite from the same organism). Chapter 8 gives an account of the whole-cell feeding experiments which strongly suggest that the primary metabolic precursors for valclavam are L-valine, L-arginine, L-methionine and glycerol. Chapter 9 reports the discovery of two enzymic activities, belonging to those of clavaminic acid synthase and proclavaminic acid amidino hydrolase, which are likely to be involved in the biosynthesis of valclavam. Together, the results of Chapters 8 and 9 point to an extensive overlap between the clavulanic acid pathway in Streptomyces clavuligerus and the valclavam pathway in Streptomyces antibioticus.
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8

Sayer, P. "The synthesis of #beta#-lactam antibiotic analogues." Thesis, Lancaster University, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235587.

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9

Templey, Margaret Patricia. "The synthesis of some new heterocyclic analogues of the beta-lactam antibiotics." Thesis, University of Bath, 1988. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.384557.

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10

Khan, Tariq Hussain. "Approaches to the synthesis of β-lactam antibiotics." Thesis, University of Edinburgh, 1987. http://hdl.handle.net/1842/12361.

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11

Deaguero, Andria Lynn. "Improving the enzymatic synthesis of semi-synthetic beta-lactam antibiotics via reaction engineering and data-driven protein engineering." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/42727.

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Semi-synthetic β-lactam antibiotics are the most prescribed class of antibiotics in the world. Chemical coupling of a β-lactam moiety with an acyl side chain has dominated the industrial production of semi-synthetic β-lactam antibiotics since their discovery in the early 1960s. Enzymatic coupling of a β-lactam moiety with an acyl side chain can be accomplished in a process that is much more environmentally benign but also results in a much lower yield. The goal of the research presented in this dissertation is to improve the enzymatic synthesis of β-lactam antibiotics via reaction engineering, medium engineering and data-drive protein engineering. Reaction engineering was employed to demonstrate that the hydrolysis of penicillin G to produce the β-lactam nucleus 6-aminopenicillanic acid (6-APA), and the synthesis of ampicillin from 6-APA and (R)-phenylglycine methyl ester ((R)-PGME), can be combined in a cascade conversion. In this work, penicillin G acylase (PGA) was utilized to catalyze the hydrolysis step, and PGA and α-amino ester hydrolase (AEH) were both studied to catalyze the synthesis step. Two different reaction configurations and various relative enzyme loadings were studied. Both configurations present a promising alternative to the current two-pot set-up which requires intermittent isolation of the intermediate, 6-APA. Medium engineering is primarily of interest in β-lactam antibiotic synthesis as a means to suppress the undesired primary and secondary hydrolysis reactions. The synthesis of ampicillin from 6-APA and (R)-PGME in the presence of ethylene glycol was chosen for study after a review of the literature. It was discovered that the transesterification product of (R)-PGME and ethylene glycol, (R)-phenylglycine hydroxyethyl ester, is transiently formed during the synthesis reactions. This never reported side reaction has the ability to positively affect yield by re-directing a portion of the consumption of (R)-PGME to an intermediate that could be used to synthesize ampicillin, rather than to an unusable hydrolysis product. Protein engineering was utilized to alter the selectivity of wild-type PGA with respect to the substituent on the alpha carbon of its substrates. Four residues were identified that had altered selectivity toward the desired product, (R)-ampicillin. Furthermore, the (R)-selective variants improved the yield from pure (R)-PGME up to 2-fold and significantly decreased the amount of secondary hydrolysis present in the reactions. Overall, we have expanded the applicability of PGA and AEH for the synthesis of semi-synthetic β-lactam antibiotics. We have shown the two enzymes can be combined in a novel one-pot cascade, which has the potential to eliminate an isolation step in the current manufacturing process. Furthermore, we have shown that the previously reported ex-situ mixed donor synthesis of ampicillin for PGA can also occur in-situ in the presence of a suitable side chain acyl donor and co-solvent. Finally, we have made significant progress towards obtaining a selective PGA that is capable of synthesizing diastereomerically pure semi-synthetic β-lactam antibiotics from racemic substrates.
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12

Law, Ka-lun, and 羅嘉倫. "Synthesis of spirolactams via phenylseleno group transfer radical cyclization and secondary amine formation via reductive aminationusing InCl3/Et3SiH promoted by Lewis acid." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39558198.

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13

Law, Ka-lun. "Synthesis of spirolactams via phenylseleno group transfer radical cyclization and secondary amine formation via reductive amination using InCl3/Et3SiH promoted by Lewis acid." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B39558198.

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14

Wang, Danni. "Synthesis and evaluation of antibacterial activity of the dual-action agents : beta-lactamase inhibitors with cytotoxic agents or beta-lactam antibiotics." Thesis, Aston University, 2001. http://publications.aston.ac.uk/12362/.

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15

Prosen, Katherine Rose. "Investigating the Mode of Action of a Novel N-sec-butylthiolated Beta-lactam Against Staphylococcus aureus." Scholar Commons, 2010. http://scholarcommons.usf.edu/etd/3609.

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N-sec -butylthioloated β-lactam (NsβL) is a novel beta-lactam antimicrobial with a mechanism of action proposed to inhibit 3-oxoacyl-acyl carrier protein synthase (ACP) III (FabH), resulting in the inhibition of fatty acid synthesis. It has been suggested that NsβL inhibits FabH indirectly by inactivating coenzyme-A (CoA). CoA is an essential cofactor for numerous proteins involved in glycolysis, the citric acid cycle (TCA), and pyruvate metabolism, in addition to fatty acid biosynthesis. This study aimed to determine the effects of NsβL on a diverse array of laboratory and clinical Staphylococcus aureus isolates by analyzing the mode of resistance in spontaneous and adaptive mutant NsβL-resistant mutants. Phenotypic analysis of the mutants was performed, as well as sequence analysis of fabH; along with comparative proteomic analysis of intracellular proteomes. Our results indicate that NsβL resistance is mediated by drastic changes in the cell wall, oxidative stress response, virulence regulation, and those pathways associated with CoA. It is our conclusion that Nsβ L has activity towards CoA, resulting in wide-spread effects on metabolism, virulence factor production, stress response, and antimicrobial resistance.
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16

Cuthbert, B. K. "Analogues of beta-lactam antibiotics." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370245.

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17

McKenna, Jeffrey M. "Asymmetric synthesis of #beta#-lactams." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240681.

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18

Rogers, M. E. "Beta-lactam antibiotics : Analysis and biosynthesis." Thesis, University of Westminster, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383031.

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19

Kang, T. W. "Novel synthesis of #beta#-lactams via radical pathways." Thesis, University of Oxford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379970.

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20

Jayaweera, G. D. S. A. "Some aspects of beta-lactam chemistry." Thesis, University of Newcastle Upon Tyne, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370619.

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21

Blackburn, Jonathan Michael. "Investigation into the biosynthesis of #beta#-lactam antibiotics." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303654.

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22

Bolister, Nina Jane. "The diffusion of beta-lactam antibiotics through biopolymers." Thesis, University of Brighton, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328209.

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23

Harris, T. A. J. "The ion-pair extraction of beta-lactam antibiotics." Thesis, London South Bank University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.279405.

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24

Badin, Sevil. "Genetic epidemiology of allergy to beta-lactam antibiotics." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/genetic-epidemiology-of-allergy-to-betalactam-antibiotics(c6571b05-3322-4662-88c4-88b300c96c9d).html.

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Background: Immediate antibiotic allergic response is an important public health problem. Genetic and molecular characterization will improve treatment outcomes for truly allergic patients, and also reduce the use (and risk of evolution of pathogen resistance) of second-line antibiotics given to patients who incorrectly believe themselves to be allergic to first-line antibiotics. Objective: To identify genetic and metabolic factors associated with allergic responses to beta-lactam antibiotics using the TwinsUK cohort and recruited participants from the Guy’s allergy clinic. Methods: The TwinsUK cohort is the largest registry of adult twins in the UK, and the Guy’s allergy clinic is an outsized clinic covering a large area of the UK. The TwinsUK cohort has been extensively molecularly characterized. After characterising the heritability, we conducted the first high-coverage genomewide association study (GWAS) between 211 self-reported cases in the TwinsUK cohort with questionnaire-defined beta-lactam allergic status and over 1000 individuals without self-reported allergic reaction to any substances. Approximately 2.1 million imputed and genotyped single nucleotide polymorphisms were investigated. A second GWAS was conducted on 48 clinically proven cases from the Guy’s Hospital allergy clinic and ~6000 population controls. In addition a metabolome-wide association study (MWAS) was conducted on the same TwinsUK registry individuals, scanning 510 different metabolites. Results: Following refinement of the self-reported beta-lactam allergy phenotype via the application of a more detailed questionnaire, we estimated a heritability of 21%. The heritability estimates provided positive evidence for a genetic component for beta-lactam allergy. A single hit from the TwinsUK GWAS at the MTHFS/BCL2A1 locus was found (p < 5x10-8 ), indicating a provisional “genomewide significant” hit. Results from the TwinsUK MWAS demonstrated that all metabolites responded as a correlated system to the differences among twins in their allergy status. There were also 4 distinct “metabolome-wide significant” hits, of which two corresponded to known metabolites, suggesting that people who had penicillin allergy had less piperine in their system in comparison with our control group and had higher amounts of 4-vinylphenol-sulfate metabolite. Conclusion: This study demonstrated a genetic component to beta-lactam allergy, and in particular provided evidence for a genetic signal at the MTFHS/BCL2A1 locus. Although the MWAS study showed that there was a metabolomic difference between the allergic and non-allergic individuals. These findings may lead to new personalised treatments based on a combination of genotyping and metabolic characterization. The findings of our studies need verification in independent cohorts.
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25

Hedberg, Maria. "[Beta]-lactam resistance in anaerobic bacteria." Stockholm : Division of Oral Microbiology, Dept. of Immunology, Microbiology, Pathology and Infectious Diseases, Hudding University Hospital, Karolinska Institute, 1995. http://catalog.hathitrust.org/api/volumes/oclc/33394040.html.

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26

Eley, A. R. "The response of Bacteroides species to beta-lactam antibiotics." Thesis, University of Nottingham, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356555.

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27

Payne, David John. "Novel aspects of transferable resistance to beta-lactam antibiotics." Thesis, University of Edinburgh, 1990. http://hdl.handle.net/1842/19226.

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Until 1983, third generation cephalosporins (3GC) were thought to be resistant to hydrolysis by all plasmid-mediated β-lactamases. However, TEM and SHV derived β-lactamases have recently evolved which can confer transferable resistance to 3GC. Six novel plasmid β-lactamases, which confer transferable resistance to 3GC have been identified and characterised. They have been compared directly to the other 3GC hydrolysing β-lactamases discovered elsewhere. The criteria implemented to distinguish these different β-lactamases were: Km and Vmax values for the hydrolysis of different substrates, molecular weight, isoelectric focusing point (pi) and susceptibility to inhibitors. The β-lactamases TEM-E1, TEM-E2, TEM-E3, and TEM-E4, were all TEM derived and, although they conferred a greater transferable resistance to ceftazidime than cefotaxime, they hydrolysed both these substrates with similar efficiencies. TEM-E2 was produced by an organism which was isolated in Liverpool in 1982 and is, consequently, the first example of transferable 3GC resistance. TEM-E3 was produced by clinical isolates from two different London hospitals, and found to be the same as IBM-10 which was discovered in the USA after the characterisation of TEM-E3. When ceftazidime was used as a selecting agent, TEM-E1 and TEM-E2, could be obtained spontaneously from a TEM-1 producing E.coli and, in the same way, TEM-E4 could be obtained from a TEM-2 producing organism. Utilising the same methodology a β-lactamase, which conferred transferable resistance to ceftazidime, was obtained from PSE-4, although such an enzyme has not yet been reported in clinical isolates. The fifth novel β-lactamase, E8825 (pi 7.9), was produced by an organism isolated in India which also produced TEM-1 and CAZ-6. This was the first example of transferable 3GC resistance in Asia and the first report of two transferable 3GC hydrolysing β-lactamases being encoded by the same plasmid. The characteristics of the sixth novel enzyme, DJP-1, suggest that it was originally an E.coli chromosomal β-lactamase. Analysis of this strain revealed that the β-lactamase (pi greater than 8.2) conferred transferable resistance to all β-lactam antibiotics and clavulanic acid. Finally, two novel methods for the isolation and purification of (3-lactamases were developed during these studies. Electro-dialysis of 0-lactamases from polyacrylamide gel allowed rapid purification of TEM-E2 from TEM-1. Fast Liquid Protein Chromatography (FPLC System) was employed to separate β-lactamase E882S from the other β-lactamases produced by the host strain. In addition it was illustrated that different β-lactam molecules can induce a variety of different β-lactamase satellite bands which can be visualized by isoelectric focusing. Moreover, it was also verified that these satellite bands were variants of the main β-lactamase protein.
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28

Reid, Alison Jean. "Resistance to beta-lactam antibiotics in gram-negative bacteria." Thesis, University of Edinburgh, 1987. http://hdl.handle.net/1842/19258.

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29

Westwood, Nicholas James. "Synthetic and mechanistic studies on the inhibition of elastases." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306872.

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30

Churcher, Ian. "Synthesis of potential pyrazolidinone-containing antibiotics." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318637.

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31

Davis, Simon Christopher. "Studies on the cleavage of sidechains from #beta#-lactam antibiotics." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315699.

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32

Bird, Juliette W. "Biosynthetic studies on the tripeptide precursor of #beta#-lactam antibiotics." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.253002.

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33

McGillivary, Angela. "Reactive solvent extraction of #beta#-lactam antibiotics and other anions." Thesis, London South Bank University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326763.

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34

Frampton, Helen Kathleen. "Studies of resistance to Beta-lactam antibiotics in Bacillus licheniformis." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328977.

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35

Crompton, I. A. "Studies on #beta#-lactamases." Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233406.

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36

Shah, Ajit Jesang. "The analysis of #beta#-lactams and their biosynthetic intermediates in fermentations of #beta#-lactam producing fungi." Thesis, University of Westminster, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.358855.

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37

Love, S. G. "Approaches to the biomimetic synthesis of β-lactam antibiotics." Thesis, University of Canterbury. Chemistry, 1986. http://hdl.handle.net/10092/7982.

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The C4 benzoyloxy substituted β-lactams (65)-(68) were formed by the copper-promoted reaction of β-lactarns (42)-(45) with t-butyl perbenzoate. The benzoyloxylation of the azetidin-2-one ring occurs at C4 with no competing reaction at the C3 position. The relative ease of abstraction by t-butoxy radicals of hydrogens bonded to the endocyclic and exocyclic carbons adjacent to the amide nitrogen was determined from the reaction of the β-lactam (47). This reaction gave the endocyclic substituted β-lactam (69), the exocyclic substituted β-lactam (70) and the disubstituted β-lactam (71). Substitution solely at the exocyclic carbon occurred in the reaction of the β-lactam (48), which gave the β-lactam (73). The mode of substitution of the β-lactams (42)-(45), (47) and (48) is discussed. Reaction of the γ-lactam (80) with t-butyl perbenzoate gave the C5 substituted γ-lactam (90) and the exocyclic substituted γ-lactam (87). The mode of formation and ratio of these two products is discussed. Bromination of N-benzoylvaline methyl ester (19) with N-bromosuccinimide, followed by reaction with tri-n-butyltin hydride gave N-benzoyl-3-bromovaline methyl ester (93). The synthesis of this compound is discussed. Reaction of 1-(1-methoxycarbonyl-2-methypropyl)azetidin-2-one (31) with sulphuryl chloride gave the azetidin-2-one (102). An independent synthesis of 1-(3-chloro-1-methoxycabonyl-2-methylpropyl)-3,3-dimethylazetidin-2-one (102) from N-(3-bromo-2,2-dimethylpropanoyl)valine methyl ester (100) is described and the mechanism of these reactions is discussed.
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38

Buckwell, S. C. "The kinetics of the #beta#-lactamase catalysed hydrolysis of cephalosporins." Thesis, University of Huddersfield, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376437.

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39

Gustavsson, Eva. "SPR biosensor analysis of [beta]-lactam antibiotics in milk : devoplement and use of assays based on a [beta]-lactam receptor protein /." Uppsala : Swedish Univ. of Agricultural Sciences, 2003. http://www.gbv.de/dms/bs/toc/363528245.pdf.

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40

Rowe, Christine Janet. "Genetic engineering of penicillin biosynthesis." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307008.

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41

Tarr, Shahida. "Using gene shuffling to increase genetic diversity in genes involved in beta-lactam biosynthesis." Thesis, Rhodes University, 2001. http://hdl.handle.net/10962/d1004074.

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The actinomycetes are gram-positive bacteria that produce more than two-thirds of the known biologically active microbial natural products, including many commercially important antibiotics, anti-cancer agents, other pharmacologically useful agents, animal health products and agrochemicals. The prevailing utilization of antibiotics continues to be the mainstay against microbial infections and a majority ofthe over six thousand antibiotics discovered thus far are from Streptomyces spp. One of the most well-characterized antibiotic biosynthetic pathway is the one involving the biosynthesis of the penicillins, cephalosporins and cephamycins. This pathway involves two initial steps which are common in filamentous fungi, lower eukaryotes and prokaryotes. The penam nucleus of penicillins and the cephem nucleus of both cephamycins andcephalosporins are formed by the condensation of the three precursor amino acids L-a-aminoadipic acid, Lcysteine and L-valine by a mechanism designated as 'non-ribosomal peptide synthesis', which involves activation and condensation of the three component amino acids and epimerization of the L- to D-valine to form a linear acyclic tripeptide called o-(L-a-aminoadipyl)-L-cysteinyl-Dvaline (ACV) by the action of a peptide synthetase. ACV is then cyclized to form isopenicillin N, an intermediate that contains an L-a-aminoadipyl side-chain attached to the penem nucleus (Fig. 1.2) by isopenicilin N synthase (IPNS or Cyclase) and this encompasses the creation of the Beta-lactam and thiazolidine rings. A broad range of ~-lactam producing Streptomyces spp were grown, the DNA extraction procedure optimised and total chromosomal DNA isolated. A bioinformatics analysis of known IPNS gene sequences allowed the synthesis of PCR primers for the iso-penicillin N synthase gene. IPNS genes and lPNS-like genes were successfully amplified from the total DNA of ten strains including two novel thermophilic strains, A. and B. Sequencing was carried out on the genes from S. hygroscopicus, S. tanashiensis and the two thermophiles A and B. This allowed development of the conditions for gene shuffiing of the IPNS gene which was carried out pairwise and resulted in the reconstitution of shuffied genes of the correct size. The resulting mixed gene sequences were cloned into the pTrcHis2-TOPO expression vector and the plasmid DNA screened and assayed for IPNS activity using HPLC which showed ten fold increase in IPNS activity as a result of the shuffiing.
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42

Thorburn, Christine Elaine. "The effect of pharmacokinetics on the development of bacterial resistance to antibiotics." Thesis, University of East London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359992.

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43

Wood, Jonathan. "Effects of garlic on the susceptibility of MRSA to beta-lactam antibiotics." Thesis, Cardiff University, 2009. http://orca.cf.ac.uk/55864/.

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It is well recognised that resistance to antibiotics is a major global health problem which is increasing in significance year on year. Many authorities believe it to be the biggest healthcare issue of the 21st century. In particular, methicillin-resistant Staphylococcus aureus (MRSA) is a major clinical problem, particularly in the UK. Plant-derived products, and particularly garlic, have been recognised as having antimicrobial activity for centuries. This traditional use has now been substantiated by credible science. Recent studies have begun to investigate whether there is any synergism between clinically-employed antimicrobials and plant-derived products, which could, in theory, make use of our currently redundant antibiotics In this study sub-MIC concentrations of garlic (MICs 1-2 mg mL-1) were shown to potentiate oxacillin susceptibility (MIC < 4 ug mL-1) against MRSA, and increase the sensitivity of MRSA to penicillin. Results suggest that increasing antibiotic susceptibility was as a result of the cumulative effects of the garlic and antibiotic rather than interaction between the two. It therefore appears that garlic does not exhibit the same mechanism of action as oxacillin or penicillin. Low concentrations of garlic (<0.5 mg mL-1), however, decreased the susceptibilities of MRSA and S. aureus to oxacillin or penicillin. Garlic caused thickening of the primary Staphylococcal cell wall, but did not damage the cell wall integrity. This is the first study to show in vitro decreasing sensitivity to garlic through repeated sub-culture in sub-inhibitory concentrations (0.5x MIC). Such isolates exhibited morphological changes but did not differ from control cultures in terms of growth dynamics. Acquired resistance to garlic has not previously been reported, suggesting these data are worthy of further investigation. The present study lends further support to the continued investigation into potentiation of antibiotic susceptibility in antibiotic-resistant organisms by phytochemicals. The results presented here do however suggest that these interactions may be more complex than anticipated and that low concentrations of phytochemicals could potentially exacerbate the problem of antibiotic-resistance.
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44

Kendall, Sharon. "An investigation of an anomalous response of E.coli to beta-lactam antibiotics." Thesis, University of Bristol, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336924.

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45

Sheppard, A. "The use of carbenoids in #beta#-lactam synthesis." Thesis, University of Manchester, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.380525.

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46

Petersson, Ann Cathrine. "Species specific susceptibility testing for [beta]-lactam antibiotics with special reference to staphylococci /." Lund : Lund University, 1998. http://catalog.hathitrust.org/api/volumes/oclc/68945092.html.

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47

Korir, Cindy Chepngeno. "Biochemical and molecular characterization of streptococcus pneumoniae strains resistant to beta-lactam antibiotics." Diss., Available online, Georgia Institute of Technology, 2004:, 2004. http://etd.gatech.edu/theses/available/etd-07062004-081519/unrestricted/korir%5Fcindy%5Fc%5F200407%5Fphd.pdf.

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Abstract:
Thesis (Ph. D.)--School of Biology, Georgia Institute of Technology, 2005. Directed by Paul Edmonds.
Paul Edmonds, Committee Chair ; Steve Harvey, Committee Member ; Igor Zhulin, Committee Member ; Yury Chernoff, Committee Member ; Mostafa El-Sayed, Committee Member. Includes bibliographical references.
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48

Leung, Yun-Chung. "Properties of mutatant derivatives of #beta#-lactamase I from Bacillus cereus." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260180.

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49

Wallace, Jeremy Iain. "Hyperinducible β-lactamase expression in gram-negative bacteria." Thesis, University of Bristol, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295568.

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50

Saunders, Geoffrey Lance. "Beta-lactam antibiotic resistance in enterobacter cloacae isolated from Groot Schuur Hospital inpatients." Thesis, University of Cape Town, 1991. http://hdl.handle.net/11427/25559.

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