合成含3-脱氧-L-艾杜糖醛酸的肝素五糖以探究抗凝血酶III结合序列的构象。

Synthesis of a 3-deoxy-L-iduronic acid containing heparin pentasaccharide to probe the conformation of the antithrombin III binding sequence.

作者信息

Lei P S, Duchaussoy P, Sizun P, Mallet J M, Petitou M, Sinaÿ P

机构信息

Ecole Normale Supérieure, Département de Chimie, URA CNRS 1686, Paris, France.

出版信息

Bioorg Med Chem. 1998 Aug;6(8):1337-46. doi: 10.1016/s0968-0896(98)00127-8.

DOI:10.1016/s0968-0896(98)00127-8

PMID:9784873

Abstract

We report in this work the total synthesis of a close analogue of the pentasaccharide active site of heparin, in which the L-iduronic acid residue has been deoxygenated at position three. 1H NMR studies demonstrated that, as anticipated, such a modification induces a shift of the conformational equilibrium toward 1C4 (contribution to the conformational equilibrium rises from 37% to 65%) and a substantial decrease of the affinity for antithrombin III (Kd 0.154 microM versus 0.050 microM).

摘要

我们在这项工作中报道了肝素五糖活性位点紧密类似物的全合成，其中L-艾杜糖醛酸残基在3位进行了脱氧。1H NMR研究表明，正如预期的那样，这种修饰导致构象平衡向1C4转移（对构象平衡的贡献从37%上升到65%），并且与抗凝血酶III的亲和力大幅降低（解离常数Kd为0.154 microM，而之前为0.050 microM）。