Synthesis of heparin-like oligosaccharides on polymer supports

• Published in: Glycoconjugate journal 2004-01, Vol.21 (5), p.179-195
• Main Authors: Ojeda, Rafael, Terentí, Olimpia, de Paz, José-Luis, Martín-Lomas, Manuel
• Format: Article
• Language: English
• Subjects: Carbohydrate Sequence; Heparan sulfate; Heparan Sulfate Proteoglycans - chemical synthesis; Oligosaccharides - chemical synthesis; Polyethylene Glycols; Polymers; Polystyrenes
• ISSN: 0282-0080; 1573-4986
• DOI: 10.1023/b:glyc.0000045091.18392.a8

The biological functions of a variety of proteins are regulated by heparan sulfate glycosaminoglycans. In order to facilitate the elucidation of the molecular basis of glycosaminoglycan-protein interactions we have developed syntheses of heparin-like oligosaccharides on polymer supports. A completely stereoselective strategy previously developed by us for the synthesis of these oligosaccharides in solution has been extended to the solid phase using an acceptor-bound approach. Both a soluble polymer support and a polyethylene glycol-grafted polystyrene resin have been used and different strategies for the attachment of the acceptor to the support have been explored. The attachment of fully protected disaccharide building blocks to a soluble support through the carboxylic group of the uronic acid unit by a succinic ester linkage, the use of trichloroacetimidates as glycosylating agents and of a functionalized Merryfield type resin for the capping process allowed for the construction of hexasaccharide and octasaccharide fragments containing the structural motif of the regular region of heparin. This strategy may facilitate the synthesis of glycosaminoglycan oligosaccharides by using the required building blocks in the glycosylation sequence.