Theoretical study of copper binding to GHK peptide

Abstract

We report ligand field molecular mechanics, density functional theory and semi-empirical studies on the binding of Cu(II) to GlyHisLys (GHK) peptide. Following exhaustive conformational searching using molecular mechanics, we show that relative energy and geometry of conformations are in good agreement between GFN2-xTB semi-empirical and B3LYP-D DFT levels. Conventional molecular dynamics simulation of Cu-GHK shows the stability of the copper-peptide binding over 100ps trajectory. Four equatorial bonds in 3N1O coordination remain stable throughout simulation, while a fifth in apical position from Cterminal carboxylate is more fluxional. We also show that the automated conformer and rotamer search algorithm CREST is able to correctly predict the metal binding position from a starting point consisting of separated peptide, copper and water.

Improved laccase production by Trametes versicolor using Copper-Glycyl-L-Histidyl-L-Lysine as a novel and high-efficient inducer

“…This could be the reasons for the best laccase production induced by GHK-Cu. In case of GHK+CuSO 4 addition, the complex GHK-Cu could be formed due to the high affinity GHK for Cu 2+ ( Alshammari and Platts, 2020 ). And thus, GHK+CuSO 4 showed partly induction effect of GHK-Cu, resulting enhanced laccase production compared to that in CuSO 4 group.…”

“…All the above results indicate that GHK-Cu was more conducive to the secretion of laccase. This fact may be due to that GHK is considered to be the transporter of metal ions through membranes, and the exchange kinetics and REDOX behavior of GHK are stable in biological systems, which makes copper much safer for cells when transported into them ( Alshammari and Platts, 2020 ). Moreover, glutathione chelating with Cu can be involved in repairing membrane damage caused by Cu ( Freedman et al, 1899 ).…”

“…GHK is non-toxic and occurs naturally in saliva, blood, and urine ( Li et al, 2016 ). Then GHK readily binds copper or zinc cations and was considered as the transporter of metal ions through membranes, which reduced the damage to cells resulted from metal ions ( Alshammari and Platts, 2020 ). In addition, GHK-Cu has antioxidant and anti-inflammatory effects, which can improve the skin and has a wide range of applications in the cosmetics and the skin tissue remodeling industry ( Pickart and Margolin, 2018 ).…”

Liposomes as Carriers of GHK-Cu Tripeptide for Cosmetic Application

“…It is a highly hydrophilic peptide that consists of three amino acids: glycine, histidine and lysine (Gly-His-Lys or GHK), with copper cations binding ability. GHK tripeptide has been found in human serum and plasma [8,9]. The amount of copper found ex vivo in human stratum corneum and the epidermis itself has been considered to be significant [10].…”