Structure-activity relationship for peptídic growth hormone secretagogues.
Ferro. P P; Krotov. G G; Zvereva. I I; Rodchenkov. G G; Segura. J J
Key Findings
- The core sequence Ala‑Trp‑(D‑Phe)‑Lys is essential for binding to the GHSR1a receptor, with specific amino‑acid positions (1, 2, 3, 7) strongly influencing potency.
- Nasal administration of GHRP‑1, GHRP‑2, GHRP‑6, Hexarelin, and Ipamorelin still produces detectable receptor activity in urine, indicating that these routes preserve bioactivity.
- Active metabolites can be identified in excreted urine, providing a way to monitor use and potential abuse of these peptides.
Practical Outcomes
- For self‑experimenters, the data suggest that keeping the Ala‑Trp‑(D‑Phe)‑Lys core intact is crucial when modifying GHRPs for personal use. Nasal delivery appears to retain enough activity to be effective, offering a non‑injectable option. Urine testing can reveal both the original peptide and its active breakdown products, which is useful for tracking dosing and compliance.
Summary
This study maps out which parts of growth‑hormone‑releasing peptides (like GHRP‑2) are needed for them to stick to the ghrelin receptor and stay active, even after they’re taken nasally. By testing different peptide tweaks and checking urine after dosing, the researchers show which chemical changes boost or reduce activity and how the body breaks the peptides down.
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.
Study Information
pubmed
2016
2016-01-26T00:00:00.000Z
10.1002/dta.1947
14
37