Structure-activity studies on prolactin-releasing peptide (PrRP). Analogues of PrRP-(19-31)-peptide

Abstract

An investigation of a series of single replacement analogues of PrRP-(19-31)-peptide has shown that good functional activity was retained when Phe31 was replaced with His(Bzl), Phe(4Cl), Nle, Trp, Cys(Bzl) or Glu(OBzl); when Val28 or Ile25 was replaced with Phg; when Gly24 was replaced with D-Ala, L-Ala, Pro or Sar; when Ser22 was replaced with Gly and when Ala21 was replaced with Thr or MeAla. The results confirm that the functionally important residues are located within the carboxyl terminal segment, -Ile-Arg-Pro-Val-Gly-Arg-Phe-NH2.

In Vivo and in Vitro Structure-Activity Relationships and Structural Conformation of Kisspeptin-10-Related Peptides

“…The essential role of the C-terminal residue was expected, because previous studies have shown the indispensable role of this amino acid to maintain an appropriate function not only of kisspeptin (Ohtaki et al, 2001;Niida et al, 2006;Orsini et al, 2007) but also of other members of the RF-amide family of peptides, which includes prolactin-releasing peptide and neuropeptide FF, where the C-terminal Arg-Phe is also critical for their biological activity (Mazarguil et al, 2001;Boyle et al, 2005). However, the native C-terminal phenylalanine residue can be replaced by different aromatic moieties, such as tyrosine, tryptophan, substituted phenylalanine, or naphthylalanine, without significant loss of potency or efficacy of Arg-Phe-amide peptides (Mazarguil et al, 2001;Boyle et al, 2005;Tomita et al, 2006). Conversely, replacement of the C-terminal phenylalanine by saturated side-chain residues such as cyclohexylalanine suppresses the biological activity of kp-10 (Orsini et al, 2007).…”

Ligand-mimicking Receptor Variant Discloses Binding and Activation Mode of Prolactin-releasing Peptide

“…1B). Although the RF-amide motif was previously identified as a major requirement for PrRP-induced agonist activity (10,11), the critical residues on the receptor remain unknown, and the ligand binding mode is still poorly understood.…”

Prolactin-releasing peptide: a new tool for obesity treatment

“…C-terminal Arg-Phe-amide sequence is critical for the preservation of biological activity of PrRP (Roland et al 1999. While C-terminal fragment of PrRP containing 13 amino acid (PrRP13) is sufficient for full binding potency to GPR10 receptor (Boyle et al 2005), PrRP analog with at least 20 amino acids is necessary for preservation of full biological activitiy in vivo ). In our previous study , we modified C-terminal Phe-amide with other bulky aromatic rings that showed not only high binding potency signaling in RC-4B/C cells comparable with or higher than those of PrRP20, but also a very significant and longlasting anorexigenic effect after central administration in fasted mice .…”