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Related Experiment Videos

Beta-C-mannosides as selectin inhibitors.

Neelu Kaila1, Lihren Chen, Bert E Thomas

  • 1Department of Chemical Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA. nkaila@war.wyeth.com

Journal of Medicinal Chemistry
|April 5, 2002
PubMed
Summary

Researchers developed novel mannose-based compounds to inhibit E- and P-selectin, crucial for inflammatory responses. Some inhibitors demonstrated superior activity compared to sLe(x) in P-selectin assays, offering potential therapeutic benefits.

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Area of Science:

  • Medicinal Chemistry
  • Biochemistry
  • Pharmacology

Background:

  • E- and P-selectin are key adhesion molecules involved in inflammatory processes.
  • Crystallographic data recently defined critical binding sites on E-selectin and P-selectin (PSGL-1 protein binding site).

Purpose of the Study:

  • To synthesize and evaluate novel mannose-based compounds as potential inhibitors of E- and P-selectin.
  • To explore a hydrophobic area on E-selectin and the PSGL-1 binding site on P-selectin.

Main Methods:

  • Solution phase parallel synthesis was employed to create three distinct libraries (A, B, C) of mannose-based compounds.
  • Biological activity was assessed using enzyme-linked immunosorbent assays (ELISA) and transferred nuclear Overhauser effect (trNOE) experiments.

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Main Results:

  • Several synthesized compounds exhibited inhibitory activity against selectins.
  • Some compounds demonstrated enhanced efficacy compared to the standard sLe(x) in P-selectin assays.

Conclusions:

  • The study successfully identified potential E- and P-selectin inhibitors based on a mannose scaffold.
  • These findings suggest promising therapeutic candidates for selectin-mediated inflammatory conditions.