ORGN 665 |
| Integrins are a widely expressed family of transmembrane &alpha/&beta heterodimeric cell surface receptors that mediate cell interaction with other cells and with extracellular matrix components. The integrin &alphav&beta3 (vitronectin receptor) is expressed on a variety of cell types, including endothelial cells, osteoclasts and vascular smooth muscle cells. &alphav&beta3 is known to be involved in osteoclast mediated bone resorption and has been implicated in tumor progression, angiogenesis and restenosis. As such, antagonists of the &alphav?3 integrin would be expected to have therapeutic potential for a variety of human diseases. Many of the known integrins, including &alphav&beta3, bind to the Arg-Gly-Asp (RGD) consensus sequence found in matrix ligands. Small molecule peptidomimetics of the RGDX sequence might, therefore, be expected to disrupt this integrin-matrix interaction in a therapeutically useful manner. We have discovered potent, small molecule RGD peptidomimetic inhibitors of &alphav&beta3. The synthetic methods developed to efficiently produce these inhibitors will be discussed.
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Technical Achievements in Organic Chemistry Awards
1:40 PM-4:55 PM, Wednesday, 13 September 2006 Moscone Center -- Room 135, Oral
Division of Organic Chemistry |