Towards a new class of synthetic antibacterials acting on lipopolysaccharide biosynthesis

Increasing antibiotic resistance in microorganisms and newly emerging patho gens has become a major problem in present society. The recent confluence o f powerful drug discovery techniques, including rational design of mechanis m-based inhibitors and combinatorial chemistry accompanied with high-throug hput screening methods, will expedite the search for new antimicrobials. Th is review article describes recent attempts in the design of selective inhi bitors of lipopolysaccharide biosynthesis, which are the target for the dev elopment of new antibiotics. The results introduced here illustrate the val ue of organic synthesis to characterize enzymatic reaction. Mechanistic pos tulates 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 usef ul structural models for elusive intermediates. (C) 2000 Wiley-Liss, Inc.