Linked Life Data

9767633

Source:http://linkedlifedata.com/resource/pubmed/id/9767633

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
1998-11-3
pubmed:abstractText
Bridged monobactams are novel, potent, mechanism-based inhibitors of class C beta-lactamases, designed using X-ray crystal structures of the enzymes. They stabilize the acyl-enzyme intermediate by blocking access of water to the enzyme-inhibitor ester bond. Bridged monobactams are selective class C beta-lactamase inhibitors, with half-inhibition constants as low as 10 nM, and are less effective against class A and class B enzymes (half-inhibition constants > 100 microM) because of the different hydrolysis mechanisms in these classes of beta-lactamases. The stability of the acyl-enzyme complexes formed with class C beta-lactamases (half-lives up to 2 days were observed) enabled determination of their crystal structures. The conformation of the inhibitor moiety was close to that predicted by molecular modeling, confirming a simple reaction mechanism, unlike those of known beta-lactamase inhibitors such as clavulanic acid and penam sulfones, which involve secondary rearrangements. Synergy between the bridged monobactams and beta-lactamase-labile antibiotics could be observed when such combinations were tested against strains of Enterobacteriaceae that produce large amounts of class C beta-lactamases. The minimal inhibitory concentration of the antibiotic of more than 64 mg/L could be decreased to 0.25 mg/L in a 1:4 combination with the inhibitor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3961-71
pubmed:dateRevised
2000-12-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Structure-based design of beta-lactamase inhibitors. 1. Synthesis and evaluation of bridged monobactams.
pubmed:affiliation
Preclinical Research, F. Hoffmann-La Roche Ltd., CH-4070 Basle, Switzerland.
pubmed:publicationType
Journal Article