Sialyl Lewis x liposomes as a multivalent ligand and inhibitor of E-selectin mediated cellular adhesion

被引:101
作者
DeFrees, SA [1 ]
Phillips, L [1 ]
Guo, L [1 ]
Zalipsky, S [1 ]
机构
[1] SEQUUS PHARMACEUT INC,MENLO PK,CA 94025
关键词
D O I
10.1021/ja954122g
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A sialyl Lewis x-PEG-DSPE derivative (3) has been prepared using a combined chemical enzymatic approach and incorporated into mPEG-DSPE containing liposomes (PEG, poly(ethylene glycol); mPEG, methoxypoly(ethylene glycol); DSPE, distearoylphosphatidylethanolamine). Several liposomal formulations of 3 were evaluated as inhibitors of E-selectin mediated cellular adhesion in an ELISA assay and were found to be similar to 750-fold more potent than the nonliposomal oligosaccharide (2) and greater than 5000-fold more potent than the natural glycotope structure (1). The dramatic increase in potency of the liposomal formulations suggests that oligosaccharide multivalency enhances inhibition of E-selectin adhesion and is an effective approach to the design of more potent selectin cell adhesion inhibitors.
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页码:6101 / 6104
页数:4
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