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Ala-scan of ghrelin (1-14): Interaction with the recombinant human ghrelin receptor

par Van Craenenbroeck, Mélanie ;Grégoire, Françoise ;De Neef, Philippe ;Robberecht, Patrick ;Perret, Jason
Référence Peptides, 25, 6, page (959-965)
Publication Publié, 2004-06

Article révisé par les pairs

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Résumé :

Ghrelin, a 28 residues acylated peptide, is the natural ligand of the growth-hormone secretagogue receptor (GHS-R), which also interacts with small synthetic peptides. We investigated the importance of each of the first 14 N-terminal residues by Ala replacement (Ala-scan) and also of the N-terminal positive charge, on the recombinant GHS-R expressed in HEK293 or CHO cells by binding, IP and Ca2+ assays. Nearly all of the replacements had no significant effect on the ligand binding or IP3/Ca2+ stimulation. Exceptions were the modification of the N-terminal residue to [A1]- or Nα-acetyl-ghrelin (1-14), confirming the requirement for the positive charge at the amino-terminus. Mutation of [F 4]- to [A4]- or [Y4]-ghrelin (1-14), were detrimental suggesting direct interaction with the GHS-R. [A8] and [Y8] were more potent than ghrelin (1-14), implying that the naturally occurring Glu8 residue may not be the optimal. © 2004 Elsevier Inc. All rights reserved.