LOW-MOLECULAR-WEIGHT HEPARINS (5-KDA) AND OLIGOHEPARINS (2-KDA) PRODUCED BY GEL-PERMEATION ENRICHMENT OR RADICAL PROCESS - COMPARISON OF STRUCTURES AND PHYSICOCHEMICAL AND BIOLOGICAL PROPERTIES

A process of chemical depolymerization of heparin initiated by free radicals has been developed. The process follows reaction kinetics of apparent first order, and it is possible to obtain heparins with different molecular weights. Low and very low molecular weight heparins (LMWHs, ≈5 kDa, and Oligo-H, ≈2 kDa) have been prepared by enriching fractions derived from natural heparin by gel permeation. The LMWHs produced by a radical reaction have been characterized by their physicochemical properties, patterns of constitutive disaccharides, NMR spectra, and biological activities in comparison with those of the LMWHs produced by an enrichment process. The process of free radical degradation is shown to produce heparins with a desired molecular weight (from 1 to > 10 kDa) without changes in their primary structure and in their physicochemical properties and with the in vitro biological activities expected for LMWHs. Furthermore, the limits of enzymatic cleavage of heparins with different molecular weights by heparinases and the possibility of obtaining a precise pattern of constitutive disaccharides are discussed. © 1992.