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

Academic Article
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Overview

authors

  • Rosen, Hugh
  • 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, John
  • Hammond, M. L.

publication date

  • January 1999

journal

  • Science  Journal

abstract

  • 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.

subject areas

  • Animals
  • Antibodies
  • Bacterial Proteins
  • Carbapenems
  • Carrier Proteins
  • Dipeptidases
  • Drug Design
  • Drug Resistance, Microbial
  • Drug Resistance, Multiple
  • Enterococcus
  • Erythrocytes
  • Haptens
  • Hexosyltransferases
  • Humans
  • Immunodominant Epitopes
  • Immunoglobulin G
  • Lactams
  • Lymphocyte Activation
  • Macaca mulatta
  • Mice
  • Mice, Inbred DBA
  • Microbial Sensitivity Tests
  • Muramoylpentapeptide Carboxypeptidase
  • Penicillin-Binding Proteins
  • Peptidyl Transferases
  • Staphylococcal Infections
  • Staphylococcus
  • Thiazoles
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Identity

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.283.5402.703

PubMed ID

  • 9924033
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Additional Document Info

start page

  • 703

end page

  • 706

volume

  • 283

issue

  • 5402

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