ORGN 278 |
| Robin Polt1, Dhanasekaran Muthu1, Edward J. Bilsky2, Henry I. Yamamura3, Frank Porreca3, Larissa Yeomans1, Charles M. Keyari1, and Richard D. Egleton3. (1) Department of Chemistry, University of Arizona, Old Chemistry Building, 1306 E. Univerisity Dr, Tucson, AZ 85721, (2) Department of Pharmacology, University of New England College of Medicine, 11 Hill Beach Road, Biddeford, ME 04005, (3) Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724 |
| O-Serine glycosyl enkephalin analogs (Tyr-D-Thr-Gly-Phe-Leu-Ser*-CONH2) and related endorphin analogs (Tyr-D-Thr-Gly-Phe-Leu-Xxx-Asn-Leu-Aib-Glu-Lys-Ala-Leu-Lys-Ser*-Leu-CONH2) have been synthesized and characterized, both conformationally and pharmacologically. Some of the glycopeptide analgesics are much more potent than morphine, and show reduced side effects. Solubility problems with the first-generation endorphin analogs have been overcome by careful design of the helical address segment. Both classes of compounds have potent mu- and delta-opioid agonist activity in vivo. CD and 2D-NMR studies show that the endorphin analogs are helical in the presence of lipid bilayers or lipid bilayer models (micelles), regardless of their glycosylation state. Transport data (BBB penetration) and antinociception data will be presented. |
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Proteins, Peptides, Amino Acids, and Nucleotides
1:00 PM-5:00 PM, Tuesday, March 30, 2004 Anaheim Convention Center -- 303D, Oral
Division of Organic Chemistry |