Development of Anti-Adhesion Carbohydrate Drugs for Clinical Use

Abstract

Specific adherence of many human pathogens is mediated by microbial adhesin proteins that recognize sugar chains attached to host cell surface glycoconjugates. More than twenty years ago a strategy was proposed for preventing or interrupting the progression of bacterial and viral infection by using soluble monosaccharides or oligosaccharides as competitive inhibitors of microbial adherence. Since then, investigations from many laboratories into the detailed structures of both microbial adhesin molecules and the carbohydrate epitopes they recognize on mammalian cells have at least partially elucidated the molecular basis for carbohydrate mediated adherence for dozens of microbial species. As new enzyme-based technologies for manufacturing oligosaccharides have emerged during the past few years, commercial scale production of oligosaccharides has become economically feasible. Proceeding from this scientific and technological platform, we are developing a class of drugs known as carbohydrate adhesion ligand homologs - inhibitors of microbial adherence comprised of free oligosaccharides chemically identical to sugar chain adhesin ligands carried on surface glycoconjugates of host mucosal cells.