Synthesis of Azaphenylglycine~4- and Aza-l-phenyl-2,3- triazole-3-alanine~4 Growth Hormone Releasing Peptide-6 and Comparison of their Conformations with AzaPhe~4GHRP-6

摘要

The replacement of an amino acid amide in a peptide by a semicarbazide affords an azapeptide, which may confer increased stability, resistance to proteases, as well as enhanced selectivity relative to the native peptide [1]. In analyses of model azapeptides using X-ray crystallography, NMR spectroscopy, and computation, preferred P-turn confonnations were observed due likely to constraints about the phi (Φ) and psi (ψ) dihedral angles, respectively from lone pair-lone pair electronic repulsion between the adjacent hydrazine nitrogen atoms and the planar geometry of the urea [1]. The conformational effects of the aza-residue in [azaPhe~4]Growth Hormone Releasing Peptide-6 (GHRP-6, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) have been suggested to account for its relative selectivity for the CD36 over the GHS-Rla receptor [2]. Studying structure-activity relationships (SARs) of [azaPhe~4]GHRP-6, new methodology for making azapeptides bearing aza-residues with aromatic side chains has been developed by a submonomer approach.