Publication Date:
1999-01-29
Description:
A carbapenem antibiotic, L-786,392, was designed so that the side chain that provides high-affinity binding to the penicillin-binding proteins responsible for bacterial resistance was also the structural basis for ameliorating immunopathology. Expulsion of the side chain upon opening of the beta-lactam ring retained antibacterial activity while safely expelling the immunodominant epitope. L-786,392 was well tolerated in animal safety studies and had significant in vitro and in vivo activities against methicillin- and vancomycin-resistant Staphylococci and vancomycin-resistant Enterococci.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosen, H -- Hajdu, R -- Silver, L -- Kropp, H -- Dorso, K -- Kohler, J -- Sundelof, J G -- Huber, J -- Hammond, G G -- Jackson, J J -- Gill, C J -- Thompson, R -- Pelak, B A -- Epstein-Toney, J H -- Lankas, G -- Wilkening, R R -- Wildonger, K J -- Blizzard, T A -- DiNinno, F P -- Ratcliffe, R W -- Heck, J V -- Kozarich, J W -- Hammond, M L -- New York, N.Y. -- Science. 1999 Jan 29;283(5402):703-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Merck Research Laboratories, Rahway, NJ 07065, USA. hugh_rosen@merck.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9924033" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibodies/blood
;
*Bacterial Proteins
;
Carbapenems/chemistry/*immunology/metabolism/*pharmacology/toxicity
;
Carrier Proteins/metabolism
;
Dipeptidases/metabolism
;
*Drug Design
;
Drug Resistance, Microbial
;
Drug Resistance, Multiple
;
Enterococcus/drug effects
;
Erythrocytes/immunology
;
Haptens
;
*Hexosyltransferases
;
Humans
;
Immunodominant Epitopes
;
Immunoglobulin G/blood
;
Lactams/chemical synthesis/chemistry/metabolism/*pharmacology
;
Lymphocyte Activation
;
Macaca mulatta
;
Mice
;
Mice, Inbred DBA
;
Microbial Sensitivity Tests
;
Muramoylpentapeptide Carboxypeptidase/metabolism
;
Penicillin-Binding Proteins
;
*Peptidyl Transferases
;
Staphylococcal Infections/drug therapy
;
Staphylococcus/drug effects
;
Thiazoles/chemical synthesis/chemistry/metabolism/*pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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