Synthesis and biological evaluation of a sialyl Lewis X mimic with significantly improved E-selectin inhibition

Authors
Thoma, G Magnani, JL Patton, JT
Citation
G. Thoma et al., Synthesis and biological evaluation of a sialyl Lewis X mimic with significantly improved E-selectin inhibition, BIOORG MED, 11(7), 2001, pp. 923-925
Citations number
24
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
7
Year of publication
2001
Pages
923 - 925
Database
ISI
SICI code
0960-894X(20010409)11:7<923:SABEOA>2.0.ZU;2-C
Abstract
The synthesis of the highly potent E-selectin inhibitor 5 is described. Sia lyl Lewis X mimic 5 was rationally designed by combining two previously dis closed beneficial sLe(x) modifications in a single molecule. The compound w as found to be 30-fold more potent than sLe(x) in a static, cell-free equil ibrium assay. Furthermore, compound 5 was highly active (IC50 = 10 muM) in a dynamic non-equilibrium assay in which sLe(x) did not inhibit neutrophil rolling at up to 1000 muM. (C) 2001 Elsevier Science Ltd. All rights reserv ed.