RESUMEN
We have synthesized three new antithrombin activating pentasaccharides displaying various sulfation patterns on the reducing end unit (H). We found that when L-iduronic acid stands in the 2S(0) conformation, the sulfate groups at positions 3 and 6 of the reducing end unit are practically devoid of influence on the activation of antithrombin. This suggests that the positive role of these sulfates is more related to their ability to shift the conformational equilibrium of L-iduronic acid towards 3S(0) than to directly interact with the protein.
Asunto(s)
Antitrombinas/química , Heparina/química , Oligosacáridos/síntesis química , Antitrombina III/química , Antitrombina III/metabolismo , Antitrombinas/metabolismo , Sitios de Unión , Conformación de Carbohidratos , Secuencia de Carbohidratos , Glicoproteínas/química , Glicoproteínas/metabolismo , Heparina/metabolismo , Ácido Idurónico/química , Ácido Idurónico/metabolismo , Sondas Moleculares , Datos de Secuencia Molecular , Oligosacáridos/metabolismo , Relación Estructura-Actividad , Sulfatos/química , Sulfatos/metabolismoRESUMEN
A single disaccharide building block is required to obtain synthetic carbohydrates that reproduce the anticoagulant activity of heparin and inhibit thrombin (n>6) and/or factor Xa (n≥2; see reaction scheme). Thus, there is evidence that heparin fragments with at least 15 saccharide units are required for thrombin inhibition. Lev=levulinoyl.