화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.287, No.1, 142-146, 2001
Structure-activity relationship of ghrelin: Pharmacological study of ghrelin peptides
Ghrelin, a novel peptide purified from the stomach, is the endogenous ligand of the growth hormone secretagogue receptor. The Sera residue of ghrelin is modified with a lipid n-octanoic acid, a modification necessary for hormonal activity. To clarify the role of acyl modification and to identify the active core of ghrelin, we examined the activities of partially digested ghrelin and synthetic ghrelin derivatives. The activities confirmed that the N-terminal portion is the active core. Moreover, synthetic ghrelin derivatives demonstrated that octanoic acid is not the only modification of the Ser(3) side chain to sustain the activity of ghrelin; other acyl acid modifications maintained activity. Amino acid replacement of Sera indicated that an L-configuration of the third residue is critical for ghrelin activity. In addition, more stable ether or thioether bonds are capable of replacing the octanoyl ester bond in ghrelin, advantageous for the generation of pharmaceuticals with longer stability.