Ramphal J Y, Hiroshige M, Lou B, Gaudino J J, Hayashi M, Chen S M, Chiang L C, Gaeta F C, DeFrees S A
Cytel Corporation, San Diego, California 92121, USA.
J Med Chem. 1996 Mar 29;39(7):1357-60. doi: 10.1021/jm9600611.
Several N-acylglucosamine derivatives of sialyl Lewis X (1-3) were prepared using a combined chemical enzymatic approach and evaluated as an inhibitor of E-selectin-mediated cellular adhesion. Compounds with aromatic functionality, 1 and 2, were found to be 3-10 times more potent than the N-acetyl derivative (14) in an ELISA E-selectin cell adhesion assay. Conformational analysis with NMR indicated that the sialyl Lewis x domain of 1 retained the conformation of the N-acetyl derivative (14) despite the presence of the N-naphthamido group. The dramatic order of magnitude increase in potency of these monovalent structures can be utilized to design more potent selectin-based cell adhesion inhibitors.
采用化学酶法联用制备了几种唾液酸化路易斯X（1-3）的N-酰基葡糖胺衍生物，并将其作为E-选择素介导的细胞黏附抑制剂进行了评估。在ELISA E-选择素细胞黏附试验中，发现具有芳香官能团的化合物1和2的效力比N-乙酰衍生物（14）高3至10倍。核磁共振构象分析表明，尽管存在N-萘甲酰胺基，化合物1的唾液酸化路易斯x结构域仍保留了N-乙酰衍生物（14）的构象。这些单价结构效力的显著数量级增加可用于设计更有效的基于选择素的细胞黏附抑制剂。
