Exploring Side-Chain Diversity by Submonomer Aza-peptide Synthesis
Organic Letters, 11(16), 3650- 3653, July 2009
David Sabatino, Ph.D. Department of Chemistry and Biochemistry
Caroline Proulx, Sophie Klocek, Carine B. Bourguet, Damien Boeglin, Huy Ong and William D. Lubell
Submonomer synthesis of aza-peptides featuring regioselective alkylation of peptide-bound aza-Gly residues provided ten aza-analogues of the Growth Hormone Releasing Peptide-6 (GHRP-6) in 15-42% yield and purity generally >or=90%. Circular dichroism demonstrated that azaPhe-peptide 7a induced a beta-turn conformation which may be responsible for its 1000-fold improvement in GHRP-6 selectivity for the CD36 receptor. This versatile method for making aza-peptides avoids solution-phase hydrazine synthesis and is well suited for studying side-chain-activity relationships of biologically active peptides.