Reduced immunotoxicity and preservation of antibacterial activity in a releasable side-chain carbapenem antibiotic

被引：31

作者：

Rosen, H ^{[1
]}

Hajdu, R ^{[1
]}

Silver, L ^{[1
]}

Kropp, H ^{[1
]}

Dorso, K ^{[1
]}

Kohler, J ^{[1
]}

Sundelof, JG ^{[1
]}

Huber, J ^{[1
]}

Hammond, GG ^{[1
]}

Jackson, JJ ^{[1
]}

Gill, CJ ^{[1
]}

Thompson, R ^{[1
]}

Pelak, BA ^{[1
]}

Epstein-Toney, JH ^{[1
]}

Lankas, G ^{[1
]}

Wilkening, RR ^{[1
]}

Wildonger, KJ ^{[1
]}

Blizzard, TA ^{[1
]}

DiNinno, FP ^{[1
]}

Ratcliffe, RW ^{[1
]}

Heck, JV ^{[1
]}

Kozarich, JW ^{[1
]}

Hammond, ML ^{[1
]}

机构：

[1] Merck Res Labs, Rahway, NJ 07065 USA

来源：

SCIENCE | 1999年 / 283卷 / 5402期

关键词：

D O I：

10.1126/science.283.5402.703

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：703 / 706

页数：4

共 21 条

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