Matches in SemOpenAlex for { <https://semopenalex.org/work/W2960608478> ?p ?o ?g. }
Showing items 1 to 75 of
75
with 100 items per page.
- W2960608478 abstract "Metallo-β-lactamases (MBLs) are a class of Zn2+ containing enzymes that hydrolyse the β-lactam bond in β-lactam antibiotics and render them inactive. New Delhi metallo-β-lactamase 1 (NDM-1) is particularly troubling as the gene blaNDM-1 is plasmid borne resulting in rapid widespread dissemination. With few effective antibiotics against NDM-1 expressing bacteria, and resistance developing to those which remain, there is an urgent need to find new MBL inhibitors.Combining β-lactam antibiotics with β-lactamase inhibitors is considered amongst the most reliable of strategies for tackling resistant pathogens. However, the development of effective β-lactamase inhibitors has proved challenging. MBLs share a conserved active site with a number of human proteins and therefore orthosteric inhibitors often result in adverse side effects.Affimers may represent an alternative for the selection of novel MBL inhibitors. An Affimer that binds NDM-1 and inhibits it in a dose dependent manner was isolated, as confirmed in β-lactamase activity assays and cell based assays in clinical strains. Initial results indicated that Affimer 21 is an allosteric inhibitor, suggesting that it may be highly specific for NDM-1, reducing the possibility of off-target effects. To elucidate the binding interaction, attempts were made at obtaining a co-crystal structure and alanine scanning mutagenesis of the two variable regions was performed. The functional effects of the alanine substitutions on efficacy of NDM-1 inhibition were measured and the data used to guide the generation of sub-libraries to select for improved inhibitors. However, despite stringent screening approaches, the original Affimer has so far proven to be the the most effective inhibitor, with an estimated IC50 of 0.37 μM.Further investigation into the use of Affimers as a platform for identifying novel inhibitors effective against metallo-β-lactamases could represent a useful tool in the ongoing battle against antibiotic resistant pathogens." @default.
- W2960608478 created "2019-07-23" @default.
- W2960608478 creator A5018202349 @default.
- W2960608478 date "2018-12-01" @default.
- W2960608478 modified "2023-09-27" @default.
- W2960608478 title "Modulation of New Delhi Metallo-β-Lactamase-1 activity using Affimers" @default.
- W2960608478 hasPublicationYear "2018" @default.
- W2960608478 type Work @default.
- W2960608478 sameAs 2960608478 @default.
- W2960608478 citedByCount "0" @default.
- W2960608478 crossrefType "dissertation" @default.
- W2960608478 hasAuthorship W2960608478A5018202349 @default.
- W2960608478 hasConcept C104317684 @default.
- W2960608478 hasConcept C107824862 @default.
- W2960608478 hasConcept C142724271 @default.
- W2960608478 hasConcept C158739034 @default.
- W2960608478 hasConcept C16318435 @default.
- W2960608478 hasConcept C166342909 @default.
- W2960608478 hasConcept C181199279 @default.
- W2960608478 hasConcept C185592680 @default.
- W2960608478 hasConcept C2780227090 @default.
- W2960608478 hasConcept C2910641391 @default.
- W2960608478 hasConcept C3020456351 @default.
- W2960608478 hasConcept C501593827 @default.
- W2960608478 hasConcept C501734568 @default.
- W2960608478 hasConcept C55493867 @default.
- W2960608478 hasConcept C70721500 @default.
- W2960608478 hasConcept C71924100 @default.
- W2960608478 hasConcept C86803240 @default.
- W2960608478 hasConcept C89423630 @default.
- W2960608478 hasConceptScore W2960608478C104317684 @default.
- W2960608478 hasConceptScore W2960608478C107824862 @default.
- W2960608478 hasConceptScore W2960608478C142724271 @default.
- W2960608478 hasConceptScore W2960608478C158739034 @default.
- W2960608478 hasConceptScore W2960608478C16318435 @default.
- W2960608478 hasConceptScore W2960608478C166342909 @default.
- W2960608478 hasConceptScore W2960608478C181199279 @default.
- W2960608478 hasConceptScore W2960608478C185592680 @default.
- W2960608478 hasConceptScore W2960608478C2780227090 @default.
- W2960608478 hasConceptScore W2960608478C2910641391 @default.
- W2960608478 hasConceptScore W2960608478C3020456351 @default.
- W2960608478 hasConceptScore W2960608478C501593827 @default.
- W2960608478 hasConceptScore W2960608478C501734568 @default.
- W2960608478 hasConceptScore W2960608478C55493867 @default.
- W2960608478 hasConceptScore W2960608478C70721500 @default.
- W2960608478 hasConceptScore W2960608478C71924100 @default.
- W2960608478 hasConceptScore W2960608478C86803240 @default.
- W2960608478 hasConceptScore W2960608478C89423630 @default.
- W2960608478 hasLocation W29606084781 @default.
- W2960608478 hasOpenAccess W2960608478 @default.
- W2960608478 hasPrimaryLocation W29606084781 @default.
- W2960608478 hasRelatedWork W1533021964 @default.
- W2960608478 hasRelatedWork W1978484656 @default.
- W2960608478 hasRelatedWork W2050152293 @default.
- W2960608478 hasRelatedWork W2071104229 @default.
- W2960608478 hasRelatedWork W2344386455 @default.
- W2960608478 hasRelatedWork W2353994932 @default.
- W2960608478 hasRelatedWork W2363190897 @default.
- W2960608478 hasRelatedWork W2750165187 @default.
- W2960608478 hasRelatedWork W2770819626 @default.
- W2960608478 hasRelatedWork W2802472264 @default.
- W2960608478 hasRelatedWork W2886433327 @default.
- W2960608478 hasRelatedWork W2901725394 @default.
- W2960608478 hasRelatedWork W2913762521 @default.
- W2960608478 hasRelatedWork W3008657815 @default.
- W2960608478 hasRelatedWork W3108325383 @default.
- W2960608478 hasRelatedWork W3108765045 @default.
- W2960608478 hasRelatedWork W3149818738 @default.
- W2960608478 hasRelatedWork W3175499591 @default.
- W2960608478 hasRelatedWork W1911015027 @default.
- W2960608478 hasRelatedWork W2799758392 @default.
- W2960608478 isParatext "false" @default.
- W2960608478 isRetracted "false" @default.
- W2960608478 magId "2960608478" @default.
- W2960608478 workType "dissertation" @default.