Studies on selectin blockers. 2. Novel selectin blocker as potential therapeutics for inflammatory disorders

Yukihisa Wada, Tadayuki Saito, Naomi Matsuda, Hiroshi Ohmoto, Kohichiro Yoshino, Masami Ohashi, Hirosato Kondo, Hideharu Ishida, Makoto Kiso, Akira Hasegawa

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Abstract

As a part of our studies of selectin blockers, we prepared 1-(2- tetradecylhexadecyl)-3'-O-sulfo Le(X) 1 and 1-(2-tetradecylhexadecyl) sLe(X) 2 and examined their inhibitory activities against natural ligand (sLe(X)) binding to E-, P-, and L-selectins. Compounds 1 and 2 were 2 times more potent than the sLe(X) tetrasaccharide toward E-selectin binding and up to 4 times more potent than sLe(X) toward P- and L-selectin binding. Interestingly, compound 1 provided dose-dependent protective effects against an immunoglobulin E-mediated skin reaction in mouse ears. This protective effect was associated with diminished tissue accumulation of neutrophils in the ear (as assessed by myeloperoxidase). These findings indicate that the modification of sLe(X) or 3'-O-sulfo Le(X) with a 'branched anchor', a 2- tetradecylhexadecyl group, is useful in the design of a more potent selectin blocker, which has broad inhibitory activities toward all selectins.

Original languageEnglish
Pages (from-to)2055-2059
Number of pages5
JournalJournal of Medicinal Chemistry
Volume39
Issue number10
DOIs
Publication statusPublished - May 10 1996
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Wada, Y., Saito, T., Matsuda, N., Ohmoto, H., Yoshino, K., Ohashi, M., ... Hasegawa, A. (1996). Studies on selectin blockers. 2. Novel selectin blocker as potential therapeutics for inflammatory disorders. Journal of Medicinal Chemistry, 39(10), 2055-2059. https://doi.org/10.1021/jm950877m