GLYCOTARGETING - THE PREPARATION OF GLYCO-AMINO ACIDS AND DERIVATIVESFROM UNPROTECTED REDUCING SUGARS

Lectins are present on the surface of many cells. Many lectins activel y recycle from membrane to endosomes and efficiently take up glycoconj ugates in a sugar-dependent manner. On this basis, glycoconjugates, sp ecially those obtained by chemical means, are good candidates as carri ers of drugs, oligonucleotides or genes. In this paper, we present a p anel of methods suitable to transform unprotected reducing oligosaccha rides into glycosynthons designed to be easily linked to therapeutic a gents. All the glycosynthons presented here are glycosylamines or deri vatives, mainly glyco-amino acids or glycopeptides. Glycosylamines are easy to obtain, but they are very labile in slightly acidic or neutra l medium; they must be stabilized, by acylation for instance. The coup ling efficiency of a reducing sugar with ammonia as well as an alkylam ine or an arylamine is higher at high temperature, however, because of the Amadori rearrangement, special conditions have to be selected to prepare the expected glycosylamine derivative with a high yield. Glyco sylamines are easily acylated by N-protected amino acids, or by haloge no acids which can then be transformed into amino acids. Alternatively , unprotected reducing oligosaccharides may very efficiently be transf ormed into N-glycosyl-amino acids and then protected by N-acylation. W ith a glutamyl derivative having both the a-amino and the gamma-carbox ylic groups free, the coupling and the acylation, which is intramolecu lar, are roughly quantitative. N-oligosaccharyl-amino acid derivatives are interesting glycosynthons, because their sugar moiety bears the s pecificity towards membrane lectins while the amino acid part has the capacity to easily substitute a therapeutic agent. ((C) Societe franca ise de biochimie et biologie moleculaire/Elsevier, Paris).