Exploring side-chain diversity by submonomer solid-phase aza-peptide synthesis.
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.
Sabatino
David
D
Université de Montréal, Department of Chemistry, C.P. 6128 Succursale Centre-Ville, Montreal, Quebec, Canada H3C 3J7.
Proulx
Caroline
C
Klocek
Sophie
S
Bourguet
Carine B
CB
Boeglin
Damien
D
Ong
Huy
H
Lubell
William D
WD
D000595:Amino Acid Sequence; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D018955:CD36 Antigens / Q000378:metabolism; D002384:Catalysis; D002942:Circular Dichroism; D020650:Combinatorial Chemistry Techniques; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D001372:Aza Compounds; D018955:CD36 Antigens; D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide