Journal article
Structure and activity of a unique heparin-derived hexasaccharide
The Journal of biological chemistry, Vol.261(31), pp.14448-14454
1986
DOI: 10.1016/S0021-9258(18)66890-5
PMID: 3771538
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, and selective irradiation were used to assign many of the NMR resonances. In addition, new techniques including sulfate determination by ion chromatography and Fourier transform IR and californium plasma desorption mass spectroscopy have been applied, resulting in an unambiguous structural assignment of 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 delta IdoA represents 4-deoxy-alpha-L-threo-hex-4-enopyranosyluronic acid, p represents pyranose, and GlcA and IdoA represent glucuronic and iduronic acid). This hexasaccharide contains a portion of the antithrombin III-binding site and has a Kd of 4 X 10(-5) M. Unlike other small heparin oligosaccharides, which are specific for coagulation factor Xa, it inhibits both factors IIa and Xa equally through antithrombin III. This hexasaccharide may have the unique capacity to act primarily through heparin cofactor II to inhibit thrombin (factor IIa) and shows over half of heparin's heparin cofactor II-mediated anti-factor IIa activity. These studies suggest the occurrence of contiguous binding sites on heparin for Xa, antithrombin III, and heparin cofactor II.
Details
- Title: Subtitle
- Structure and activity of a unique heparin-derived hexasaccharide
- Creators
- R. J LINHARDT - Univ. Iowa, coll. pharmacy, Iowa City IA 52242, United StatesK. G RICE - Univ. Iowa, coll. pharmacy, Iowa City IA 52242, United StatesZ. M MERCHANT - Univ. Iowa, coll. pharmacy, Iowa City IA 52242, United StatesY. S KIM - Univ. Iowa, coll. pharmacy, Iowa City IA 52242, United StatesD. L LOHSE - Univ. Iowa, coll. pharmacy, Iowa City IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.261(31), pp.14448-14454
- DOI
- 10.1016/S0021-9258(18)66890-5
- PMID
- 3771538
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology; Bethesda, MD
- Language
- English
- Date published
- 1986
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984065500502771
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