화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.284, No.3, 655-659, 2001
Structural similarity of ghrelin derivatives to peptidyl growth hormone secretagogues
Ghrelin is a 28-amino acid residue endogenous growth hormone secretagogue, Intensive investigations revealed that the N-terminus tetrapeptide, having octanoyl group at Sers, is the minimum active core. In this study, we further explored the structure-function relationships of the active N-terminus portion of ghrelin using a Ca2+ mobilization assay. The smallest and most potent ghrelin derivative we have found so far is 5-aminopentanoyl-Ser(Octyl)-Phe-Leu-aminoethylamide, showing comparable activity to the natural molecule, In the process of modifying the active core, the ghrelin-derived short analogues emerged structurally close to peptidyl growth hormone secretagogues. The N-terminus modification suggested that Gly(1)-Ser(2) unit works as a spacer, forming adequate distance between N-alpha-amino group and n-octanoyl group. Replacement of 3rd and 4th amino acid residues to D-isomer suggested that the N-terminal dipeptide contributes to shape the biologically active geometry by effecting conformation of residues in positions 3 and 4.