Enzymatic preparation of heparin disaccharides as building blocks in glycosaminoglycan synthesis

Pharmaceutical heparin and heparan sulfate, isolated from a side-stream of a commercial heparin manufacturing process, have been enzymatically depolym erzed with heparin lyases obtained from Flavobacterium heparinun. Heparin a fforded a trisulfated disaccharide product that was recovered from the reac tion mixture using gel permeation chromatography. Heparan sulfate afforded unsulfated disaccharide that was conveniently recovered from the product mi xture by ion exchange chromatography. Both disaccharides were obtained in g ram amounts at 90% or higher purity. Both enzymatically prepared disacchari des were chemically protected to prepare building blocks required for the f uture chemical synthesis of therapeutically valuable heparin oligosaccharid es.