Aza-amino acid scan for rapid identification of secondary structure based on the application of N-Boc-aza(1)-dipeptides in peptide synthesis.
Azapeptides, peptide analogues in which the alpha-carbon of one or more of the amino acid residues is replaced with a nitrogen atom, exhibit propensity for adopting beta-turn conformations. A general protocol for the synthesis of azapeptides without racemization on solid phase has now been developed by introducing the aza-amino acid residue as an N-Boc-aza(1)-dipeptide. This approach has been validated by the synthesis of six N-Boc-aza(1)-dipeptides and their subsequent introduction into analogues of the C-terminal peptide fragment of the human calcitonin gene-related peptide (hCGRP). By performing an aza-amino acid scan of such antagonist peptides, a set of aza-hCGRP analogues was synthesized to examine the relationship between turn secondary structure and biological activity.
Melendez
Rosa E
RE
Département de Chimie, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, Québec H3C 3J7, Canada.
Lubell
William D
WD
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D015740:Calcitonin Gene-Related Peptide / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010452:Peptide Biosynthesis; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017433:Protein Structure, Secondary
D000596:Amino Acids; D001372:Aza Compounds; D004151:Dipeptides; D006834:Hydrazines; D010455:Peptides; D015740:Calcitonin Gene-Related Peptide