| Vidya Prasad1, Angie R. Angeles1, John Hynes Jr.1, Gary G. Chicchi2, Elizabeth T. Birzin2, Marc Kurtz2, Dennis J. Underwood3, Edward R. Thornton1, Amos B. Smith III1, and Ralph Hirschmann1. (1) Department of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, PA 19104, (2) Merck Research Laboratories, Rahway, NJ 07065, Rahway, NJ 07065, (3) Infinity Pharmaceuticals, Cambridge, MA 02139, 760 Memorial Dr, Cambridge, MA 02139 |
| Monosaccharide-based peptidomimetics typified by (+)-1 have been shown by the Hirschmann/Smith collaboration to mimic the β-turn of SRIF. The side chains of (+)-1 at C2, C1 and C6 mimic Phe7, D-trp8 and Lys9 of SRIF. In addition, (+)-1, also binds the NK1 receptor as an antagonist, but via different side chains. To investigate the importance of the pyranose oxygen in binding, we have explored the carbacycle (+)-2. We also investigated catechol 3 as a scaffold for β-turn mimicry. Replacement of Phe7 of SRIF with Ala7 was reported by Rivier to cause a 97% loss of activity. However, removal of the Phe7 mimicking side chain on the catechol scaffold 3 produced no loss in affinity. This observation led us to probe possible interactions between the benzene ring of the scaffold and the receptor. Exploitation of new scaffolds toward the understanding of their role in ligand-receptor interaction will be described. 
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New Reactions, Methodology, Heterocycles, Aromatics
8:00 PM-10:00 PM, Wednesday, August 25, 2004 Pennsylvania Convention Center -- Hall D, Poster
Sci-Mix
8:00 PM-10:00 PM, Monday, August 23, 2004 Pennsylvania Convention Center -- Hall D, Sci-Mix
Division of Organic Chemistry
The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004
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