A1 Refereed original research article in a scientific journal
Small molecule designed to target metal binding site in the alpha 2I domain inhibits integrin function
Authors: Kapyla J, Pentikainen OT, Nyronen T, Nissinen L, Lassander S, Jokinen J, Lahti M, Marjamaki A, Johnson MS, Heino J,
Publisher: AMER CHEMICAL SOC
Publication year: 2007
Journal: Journal of Medicinal Chemistry
Journal name in source: JOURNAL OF MEDICINAL CHEMISTRY
Journal acronym: J MED CHEM
Volume: 50
Issue: 11
First page : 2742
Last page: 2746
Number of pages: 5
ISSN: 0022-2623
DOI: https://doi.org/10.1021/jm070063t(external)
Web address : http://pubs.acs.org/doi/abs/10.1021/jm070063t(external)
Abstract
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.
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.
Research Areas
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