Structure based drug design of potent inhibitors of CTX-M9 class A β-Lactamases in Aotearoa (New Zealand).

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dc.contributor.advisor Squire, C en Bhatia, Sunny en 2015-01-28T21:03:43Z en 2014 en
dc.identifier.citation 2014 en
dc.identifier.uri en
dc.description Full text is available to authenticated members of The University of Auckland only. en
dc.description.abstract Multidrug-resistant strains possessing extended-spectrum β-Lactamases (ESBLs) have antimicrobial resistance against large variety of β-Lactam antibiotics. The widespread emergence of resistance to antibiotics in pathogenic bacteria over the past decade has narrowed our selection of the available therapeutic options creating a challenging situation. β- Lactams are the largest and most generally used group of antimicrobial agents worldwide and bacterial isolates of the Enterobacteriaceae have become resistant to almost all the antimicrobial drugs including third generation cephalosporins and also have resistance against cefotaxime, ceftriaxone and ceftazidime. In the past decade, CTX-M enzymes have become the most prevalent and predominant ESBLs in hospital and community settings through the mobilization of blaCTX-M genes. The speed with which the newest resistance genes, including CTX-M β-Lactamases, have circulated among the different gram negative species around the world is now considered a global public health crisis. Understanding the impact of resistance against antimicrobial agents is a critical step to resolve the scope of the problem and find appropriate strategies to control the spread of resistant organisms, which have raised the overall treatment cost. The aim of this thesis was to express CTX-M9 protein, which is involved in hydrolysing cefotaxime and to solve the structure of CTX-M9 to use for fragment screening and design of novel inhibitors to treat antibacterial resistance. Protein structure based approaches were implemented to discover fragments/drugs with novel modes of action and a few fragments have been observed with strong interactions in the active site, which could be vital to meet the threats created by the emergence of resistant organisms. Attempts to solve the crystal structure of CTX-M9 serine active site with fragments were not successful. However, new methodologies were used to remove unwanted phosphate anion from the serine active site, which can be helpful for the drug designers to solve crystal structures with drug molecules. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof Masters Thesis - University of Auckland en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights Restricted Item. Available to authenticated members of The University of Auckland. en
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dc.rights.uri en
dc.title Structure based drug design of potent inhibitors of CTX-M9 class A β-Lactamases in Aotearoa (New Zealand). en
dc.type Thesis en The University of Auckland en Masters en
dc.rights.holder Copyright: The Author en
pubs.elements-id 474136 en
pubs.record-created-at-source-date 2015-01-29 en
dc.identifier.wikidata Q112904581

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