Structure and activity of a unique heparin-derived hexasaccharide.

摘要: Abstract A hexasaccharide representing a major sequence in porcine mucosal heparin has been enzymatically prepared from heparin. Its structure was determined by an integrated approach using chemical, enzymatic, and spectroscopic methods. Two-dimensional 1H homonuclear COSY, C-H correlation NMR, selective irradiation were used to assign many of the NMR resonances. In addition, new techniques including sulfate determination ion chromatography Fourier transform IR californium plasma desorption mass spectroscopy have applied, resulting unambiguous structural assignment delta IdoAp2S(1----4)-alpha-D-GlcNp2S6S(1----4)-alpha-L-IdoAp++ +(1----4)-alpha-D-GlcNA cp6S-(1----4)-beta-D-GlcAp(1----4)-alpha-D-GlcNp2S3S6S (where IdoA represents 4-deoxy-alpha-L-threo-hex-4-enopyranosyluronic acid, p pyranose, GlcA represent glucuronic iduronic acid). This contains portion antithrombin III-binding site Kd 4 X 10(-5) M. Unlike other small oligosaccharides, which are specific for coagulation factor Xa, it inhibits both factors IIa Xa equally through III. may unique capacity act primarily cofactor II inhibit thrombin (factor IIa) shows over half heparin's II-mediated anti-factor activity. These studies suggest occurrence contiguous binding sites on III, II.