# Growth Hormone–Releasing Peptides: Investigation of Their Secondary Structure, Thermal Stability, and Model Membrane Interactions

## TL;DR

This paper studies eight growth hormone-releasing peptides using a technique called ECD to understand their structure and interactions with model membranes.

## Contribution

This is the first systematic study of GHRPs using ECD and TD-DFT to analyze their conformational preferences and membrane interactions.

## Key findings

- ECD spectroscopy revealed similarities and differences in the secondary structures of eight GHRPs.
- Interactions with SDS micelles caused notable ECD changes, especially for GHRP-5, suggesting α-helical structure formation.
- TD-DFT calculations confirmed the conformational changes induced by membrane interactions.

## Abstract

Growth hormone–releasing peptides (GHRPs) comprise a group of small synthetic peptides that can effectively influence growth hormone secretion both in humans and animals. As many health conditions are associated with growth hormone dysregulation, this class of compounds seems to be good candidates for various therapeutic purposes. However, GHRPs are also associated with doping in professional sports and they have been abused by amateur sportsmen and bodybuilders as well. In the present work, we investigated eight GHRPs by electronic circular dichroism (ECD) spectroscopy, which is inherently sensitive to the secondary structure of peptides and proteins. We stressed similarities and differences in their ECD spectra with respect to the similarities and differences of their respective chemical structures. We also studied interactions of the selected compounds with a model membrane system consisting of sodium dodecyl sulfate (SDS) micelles. The most interesting ECD spectral changes were observed for the GHRP‐5—SDS micelles system, where the induced ECD signal indicated the formation of α‐helical‐like secondary structure. To address the observed phenomena, conformational search with subsequent ECD spectra calculation at the time‐dependent density functional theory (TD‐DFT) level was performed to clarify the secondary structure changes. To the best of our knowledge, this is the first work where such a broad ensemble of GHRPs was systematically studied by ECD and the achieved results document that this approach provides a suitable analytical tool not only for a description of their natural conformational preferences, but can also bring insight into their possible interactions with the surrounding environment.

Eight growth hormone–releasing peptides were analyzed by electronic circular dichroism spectroscopy, including evaluation of their thermal stability and interactions with model membranes. In the selected case, occurring interactions were successfully described by the density functional theory calculations, revealing how model membranes affected conformational preferences.