title: Experimental proof for the structure of a thrombin-inhibiting heparin molecule.
abstract: Kinetic studies of thrombin inhibition by antithrombin in the presence of heparin have shown that thrombin binds to heparin in a preformed heparin-antithrombin complex. To study the relative position of the thrombin binding domain and the antithrombin binding domain on a heparin molecule we have designed and synthesized heparin mimetics, which structurally are very similar to the genuine polysaccharide. Their inhibitory properties with respect to factor Xa and thrombin provide experimental evidence that in heparin the thrombin binding domain must be located at the nonreducing end of the antithrombin binding domain to observe thrombin inhibition. As expected, factor Xa inhibition is not affected by elongation of the antithrombin binding pentasaccharide sequence, regardless of the position in which this elongation takes place.
authors: Département Cardiovasculaire/Thrombose Sanofi-Synthélabo, Toulouse, France. maurice.petitou@sanofi-synthelabo.com
authors: M
authors: M
authors: Petitou
authors: A
authors: A
authors: Imberty
authors: P
authors: P
authors: Duchaussoy
authors: P A
authors: PA
authors: Driguez
authors: M L
authors: ML
authors: Ceccato
authors: F
authors: F
authors: Gourvenec
authors: P
authors: P
authors: Sizun
authors: J P
authors: JP
authors: Hérault
authors: S
authors: S
authors: Pérez
authors: J M
authors: JM
authors: Herbert
mesh_terms: D000991:Antithrombins / Q000138:chemical synthesis / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006493:Heparin / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data
chemical_list: D000991:Antithrombins; D006493:Heparin