Peptides Binding to the Hunger Hormone Ghrelin

Abstract

The neutralisation of circulating ghrelin, the only known peripheral orexigenic peptide hormone, is a promising approach for the pharmacological treatment of obesity. To select peptides with an affinity towards ghrelin, 4 selection procedures were carried out with random peptide phage display libraries Ph.D.-7 and Ph.D.-12. Due to the absence of a common consensus motif, a stepwise elimination approach was used. The pool of selected peptides displaying phage clones was thoroughly examined to remove any potential target-unrelated peptides. The affinity of the remaining phage clones for ghrelin was tested with ELISA. An analysis of the binding properties revealed four-phage displayed peptides that bind to ghrelin with moderate affinity, with ADTVPRH and MEMKKTHPVLGA being the most specific. Additional advantage of peptide MEMKKTHPVLGA is an indication of binding to octanoyl group on N-terminal part of ghrelin, involved in receptor interaction. Hence peptide MEMKKTHPVLGA represents the most suitable lead for further investigation.

Key words

ghrelin - des-acyl ghrelin - phage display - neutralising peptides

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