Optimization of the pharmaceutical profile of the anti-HIV-1 fusion inhibitory protein, PSC-RANTES

ORGN 219

Les P. Miranda1, H. Shao2, J. Williams2, S-Y. Chen2, T. Kong2, R. Garcia2, Y. Chinn2, N. Fraud2, Jay Ye2, Jill Wilken2, D. Low2, N. Cagle2, M. Carnevali2, A. Lee2, D. Song2, A. Kung2, J. A. Bradburne2, X. Paliard2, and G. Kochendoerfer2. (1) Gryphon Therapeutics, 600 Gateway Boulevard, South San Franciso, CA 94080; currently at Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, (2) Gryphon Therapeutics, 600 Gateway Boulevard, South San Francisco, CA 94080
A combination of non-coded and coded amino acid mutagenesis, peptide-backbone engineering, and site-specific polymer modification was used to alter the oligomerization state, circulating lifetime, signaling, and anti-HIV activity of PSC RANTES. Several polymer-modified analogues were designed, and prepared by total chemical synthesis. The sequences of these analogues differed from PSC-RSANTES in the N-terminal and C-terminal regions, and also in regards to the polymer attachment site. The results of this work will be discussed here.
 

Ralph F. Hirschmann Award in Peptide Chemistry
1:30 PM-5:00 PM, Monday, 27 March 2006 Georgia World Congress Center -- C303/304/305, Oral

Division of Organic Chemistry

The 231st ACS National Meeting, Atlanta, GA, March 26-30, 2006