从蛋黄中酶促合成唾液酸化路易斯X二聚体作为E选择素抑制剂。

Enzymatic synthesis of a sialyl Lewis X dimer from egg yolk as an inhibitor of E-selectin.

作者信息

Lin C H, Shimazaki M, Wong C H, Koketsu M, Juneja L R, Kim M

机构信息

Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.

出版信息

Bioorg Med Chem. 1995 Dec;3(12):1625-30. doi: 10.1016/0968-0896(95)00150-6.

DOI:10.1016/0968-0896(95)00150-6

PMID:8770386

Abstract

A dimeric sialyl Lewis X (SLex) glycopeptide was synthesized enzymatically in three steps from an N-linked oligosaccharide prepared from egg yolk. Treatment of delipidated hen egg yolk with the protease Orientase and neuraminidase gave a dimeric N-acetyllactosamine-containing oligosaccharide linked to asparagine. Addition of sialic acid and fucose catalyzed by alpha-2,3-sialyltransferase and alpha-1,3-fucosyltransferase provided the dimeric SLex, which was shown to be as active as monomeric SLex as an inhibitor of E-selectin with IC50 0.75 mM. The synthetic dimeric SLex of the mucin type (i.e. SLex linked to the 3- and 6-OH groups of Gal) is, however, about five times as active as the monomer. It is suggested that dimeric SLex glycopeptides of the mucin type would be effective ligands for E-selectin.

摘要

一种二聚体唾液酸化路易斯X（SLex）糖肽由蛋黄制备的N-连接寡糖经三步酶促合成。用蛋白酶Orientase和神经氨酸酶处理脱脂鸡蛋黄，得到与天冬酰胺相连的含二聚体N-乙酰乳糖胺的寡糖。由α-2,3-唾液酸转移酶和α-1,3-岩藻糖转移酶催化添加唾液酸和岩藻糖，得到二聚体SLex，其作为E-选择素抑制剂的活性与单体SLex相同，IC50为0.75 mM。然而，粘蛋白型的合成二聚体SLex（即与Gal的3-和6-OH基团相连的SLex）的活性约为单体的五倍。有人提出，粘蛋白型二聚体SLex糖肽将是E-选择素的有效配体。