Extension and structural variability of the antithrombin-binding sequence in heparin.

摘要: Oligosaccharides with different affinities for antithrombin were isolated following partial deaminative cleavage of pig mucosal heparin nitrous acid. The smallest high-affinity component obtained was previously identified as an octasaccharide the predominant structure: (Formula: see text). interaction this octasaccharide, and deca- dodecasaccharides containing same sequence, studied by spectroscopic techniques. near-ultraviolet difference spectra, circular dichroism fluorescence enhancements induced adding these oligosaccharides to differed only slightly from corresponding parameters measured in presence undegraded heparin. Moreover, binding constants similar (1.0-2.9 X 10(7) M-1 at I = 0.3). In contrast, two hexasaccharides units 1-6 3-8, respectively, above sequence showed about a 1000-fold lower affinity antithrombin, also considerably spectral perturbations antithrombin. Since hexasaccharide contains reducing-terminal anhydromannose residue instead N-sulfated glucosamine unit 6 intact results strongly support our previous conclusion that N-sulfate group position is essential low 3-8 provides further evidence pentasaccharide 2-6 constitutes actual antithrombin-binding region molecule. Structural analysis various revealed natural variants substituted N-acetyl 2. preponderance over groups may be rationalized terms mechanism biosynthesis, assuming D-gluco configuration 3 feature region.