Towards a new class of synthetic antibacterials acting on lipopolysaccharide biosynthesis

Abstract

Increasing antibiotic resistance in microorganisms and newly emerging pathogens has become a major problem in present society. The recent confluence of powerful drug discovery techniques, including rational design of mechanism-based inhibitors and combinatorial chemistry accompanied with high-throughput screening methods, will expedite the search for new antimicrobials. This review article describes recent attempts in the design of selective inhibitors of lipopolysaccharide biosynthesis, which are the target for the development of new antibiotics. The results introduced here illustrate the value of organic synthesis to characterize enzymatic reaction. Mechanistic postulates have pointed the way to the design of potent inhibitors, and these in turn have provided insight into details of the reaction, as well as useful structural models for elusive intermediates. Drug Dev. Res. 50:416–424, 2000. © 2000 Wiley-Liss, Inc.