Synthesis of Peptide-Based Trivalent Scaffold for Preparation of Cluster Glycosides

Abstract

Publisher Summary The presence of two or more sugar residues, which are the recognition target of lectins on one ligand molecule, can sometimes bring about a large enhancement in binding affinity. A number of high-affinity, di- and trivalent inhibitors were prepared, using an amino acid- or peptide-based scaffold to provide branching points—aspartic acid having two carboxylic acid groups as a divalent scaffold and γ -L-glutamyl-L-glutamic acid having three carboxylic acid groups as a trivalent scaffold. ω-amino-terminated glycosides are attached to these scaffolds to produce, respectively, di- and trivalent glycosides conveniently. Advantages of peptide-based scaffolds are the existence of well-established synthetic peptide chemistry and the easy availability of ω -aminoglycosides and glycosylamines via synthesis or from natural sources. An alternative scaffold, β -L-aspartyl-L-aspartic acid, which can be prepared by an easy synthetic scheme without involving any chromatographic separations, was used instead of expensive counterparts like γ-glutamylglutamic acid. This new scaffold was used for the synthesis of a trivalent mammalian hepatic lectin inhibitor and was found to be as effective as the derivatives based on γ-glutamylglutamic acid.