Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 50, Issue 11, Pages 2742-2746Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm070063t
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Integrin alpha 2 beta 1 is a potential target molecule in drug development. We have established design criteria for molecules that bind to the closed conformation of alpha 2I domain via Mg2+ in MIDAS (metal ion dependent adhesion site) while simultaneously forming interactions with neighboring amino acid residues. Specific tetracyclic Streptomyces products belonging to the group of aromatic polyketides fulfill our criteria and inhibit alpha 2 beta 1 integrin. All previously described inhibitors of alpha I domain integrins act in an allosteric manner.
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