Studies on selectin blocker. 3. Investigation of the carbohydrate ligand sialyl Lewis X recognition site of P-selectin

Yasuyuki Hiramatsu, Hideki Tsujishita, Hirosato Kondo

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We have previously found that a 1-deoxy sialyl Lewis X (3), which lacks only the C-1 hydroxyl group of sialyl Lewis X (sLe(X)), exhibited up to 20 times more potency than the sLe(X) toward P-selectin binding. In order to explain the structure-activity relationship, we constructed structural models of the complexes of P-selectin and compounds 1-3 and sLe(X). From the modeling analysis, we found that the carbonyl oxygen of the N-acetyl group of GlcNAc in 3 formed a hydrogen bond with the amide group of Asn 82 in P- selectin. We also supposed that there was a hydrophobic interaction between the pyranose of GlcNAc in compound 3 and the imidazole ring of His 108 in P- selectin. However, it is considered that those interactions would not be appreciable in the case of sLe(X) or other 1-deoxy sLe(X) analogs (1,2). Accordingly, our results could be helpful in obtaining a new concept to design a potent inhibitor toward P-selectin binding.

Original languageEnglish
Pages (from-to)4547-4553
Number of pages7
JournalJournal of Medicinal Chemistry
Volume39
Issue number23
DOIs
Publication statusPublished - Nov 26 1996
Externally publishedYes

Fingerprint

Selectins
P-Selectin
Carbohydrates
Ligands
Structural Models
Structure-Activity Relationship
Hydrophobic and Hydrophilic Interactions
Amides
Hydroxyl Radical
Hydrogen
Oxygen

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Studies on selectin blocker. 3. Investigation of the carbohydrate ligand sialyl Lewis X recognition site of P-selectin. / Hiramatsu, Yasuyuki; Tsujishita, Hideki; Kondo, Hirosato.

In: Journal of Medicinal Chemistry, Vol. 39, No. 23, 26.11.1996, p. 4547-4553.

Research output: Contribution to journalArticle

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