Linked Life Data

20929256

Source:http://linkedlifedata.com/resource/pubmed/id/20929256

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2010-11-4
pubmed:abstractText
We report the synthesis and biochemical evaluation of several selective inhibitors of class II (zinc dependent) fructose bis-phosphate aldolases (Fba). The products were designed as transition-state analogues of the catalyzed reaction, structurally related to the substrate fructose bis-phosphate (or sedoheptulose bis-phosphate) and based on an N-substituted hydroxamic acid, as a chelator of the zinc ion present in active site. The compounds synthesized were tested on class II Fbas from various pathogenic microorganisms and, by comparison, on a mammalian class I Fba. The best inhibitor shows K(i) against class II Fbas from various pathogens in the nM range, with very high selectivity (up to 10(5)). Structural analyses of inhibitors in complex with aldolases rationalize and corroborate the enzymatic kinetics results. These inhibitors represent lead compounds for the preparation of new synthetic antibiotics, notably for tuberculosis prophylaxis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7836-42
pubmed:dateRevised
2011-11-14
pubmed:meshHeading
pubmed-meshheading:20929256-Animals, pubmed-meshheading:20929256-Anti-Bacterial Agents, pubmed-meshheading:20929256-Antifungal Agents, pubmed-meshheading:20929256-Antitubercular Agents, pubmed-meshheading:20929256-Crystallography, X-Ray, pubmed-meshheading:20929256-Drug Design, pubmed-meshheading:20929256-Fructose-Bisphosphate Aldolase, pubmed-meshheading:20929256-Fructosediphosphates, pubmed-meshheading:20929256-Hydroxamic Acids, pubmed-meshheading:20929256-Inhibitory Concentration 50, pubmed-meshheading:20929256-Kinetics, pubmed-meshheading:20929256-Microbial Sensitivity Tests, pubmed-meshheading:20929256-Models, Molecular, pubmed-meshheading:20929256-Rabbits, pubmed-meshheading:20929256-Structure-Activity Relationship, pubmed-meshheading:20929256-Sugar Phosphates, pubmed-meshheading:20929256-Zinc
pubmed:year
2010
pubmed:articleTitle
Rational design, synthesis, and evaluation of new selective inhibitors of microbial class II (zinc dependent) fructose bis-phosphate aldolases.
pubmed:affiliation
ECBB, ICMMO, Univ Paris-Sud, UMR 8182, F-91405 Orsay, France.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural