Structure‐activity relationship for peptídic growth hormone secretagogues

Abstract

Growth hormone releasing peptides (GHRPs) could be widely used by cheating athletes because they produce growth hormone (GH) secretion, so may generate an ergogenic effect in the body. Knowledge of the essential amino acids needed in GHRP structure for interaction with the target biological receptor GHSR1a, the absorption through different administration routes, and the maintenance of pharmacological activity of potential biotransformation products may help in the fight against their abuse in sport. Several GHRPs and truncated analogues with the common core Ala-Trp-(D-Phe)-Lys have been studied with a radio-competitive assay for the GHSR1a receptor against the radioactive natural ligand ghrelin. Relevant chemical modifications influencing the activity for positions 1, 2, 3, and 7 based on the structure aa-aa-aa-Ala-Trp-(D-Phe)-Lys have been obtained. To test in vivo the applicability of the activities observed, the receptor assay activity in samples from excretion studies performed after nasal administration of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin was confirmed. Overall results obtained allow to infer structure-activity information for those GHRPs and to detect GHSR1a binding (intact GHRPs plus active metabolites) in excreted urines. Copyright © 2016 John Wiley & Sons, Ltd.

Detection of Growth Hormone Releasing Peptides in Serum by a Competitive Receptor Binding Assay

“…For GHRP-6, the detection windows obtained here in serum and previously in urine [39] samples were very similar, so it also would be very interesting to study other GHRPs…”

“…The detection time window for GHRP-2 appeared shorter in serum as the drug can be detected for 8 h after administration in serum versus 18 h in urine samples [39]. For GHRP-6, the detection windows obtained here in serum and previously in urine [39] samples were very similar, so it also would be very interesting to study other GHRPs…”

Fully automated dried blood spot sample preparation enables the detection of lower molecular mass peptide and non-peptide doping agents by means of LC-HRMS

“…After intravenous (i.v.) administration of GHRP-2, detection times appeared shorter in serum than in urine samples, but for GHRP-6, detection windows were found to be comparable in both matrices [21,22]. Nevertheless, for urine analysis, knowledge about the metabolic fate of peptide drugs is desirable as the presence of metabolites alongside the intact and unmodified drug (candidate) was shown in the past [3,9,23].…”

Identification of a novel growth hormone releasing peptide (a glycine analogue of GHRP‐2) in a seized injection vial

“…An important question is if this identified peptide possesses GH releasing ability. Ferro et al published the research in which the affinity for ghrelin receptor of different GHRPs and potential metabolites has been studied. On the basis of their results, it can be stated that the target compound demonstrates several essential properties which enable strong receptor interaction: a core of three amino acids in the following order – Ala‐Trp‐Phe; alanine at position 2; and β‐naphthylalanine at position 3 and lysine with amidated carbonyl group at C‐terminal position.…”