Scanning of GHRP-6 with aza-amino acids

WCC 17

Caroline Proulx,, Damien Boeglin, and William D. Lubell, Department of Chemistry, Université de Montréal, C.P. 6128, Succursale Centre Ville, Montréal, QC H3C 3J7, Canada
Aza-aminoacids are amino acids in which the á-carbon is replaced with a nitrogen atom. When they are introduced into peptide structures, aza-amino acid have been shown by X-ray diffraction, NMR spectroscopy and computational analysis to induce turn conformations. Growth hormone-releasing peptides (GHRPs) are a class of synthetic peptides known to stimulate GH release through binding of a G-protein coupled receptor known as GHS-R2. Orally active GHS-R ligands have been pursued as rejuvenating anabolic treatments of somatopause, as well as potential therapeutic agents for obesity. The relationship between the conformation and activity of GHRP-6 [His-D-Tryp-Ala-Trp-D-Phe-Lys-NH2] has been explored by the synthesis of a set of aza-peptides in which each residue has been replaced by an aza-amino acid counterpart. Further examination of the most potent aza-peptide analogs has been performed by an alanine scan to elucidate the structural requirements for activity. Our presentation will highlight the solid-phase synthesis protocols that we have developed for creating libraries of aza-peptides for aza-amino acid scanning, the biological activity of the aza-peptide analogs of GHRP-6 and a model for their biologically active conformation.

The Merck Index Women in Chemistry
2:30 PM-4:30 PM, Monday, August 18, 2008 Pennsylvania Convention Center -- Hall C, Poster

Women Chemists Committee

The 236th ACS National Meeting, Philadelphia, PA, August 17-21, 2008