Anti-aging activity of Syn-Ake peptide by in silico approaches and in vitro tests

Abstract

The increase in the aging population worldwide has led scientists to turn to research to prevent the aging process. In this context, synthetic peptides emerge as candidate molecules for developing new anti-aging products. This study aims to investigate the possible interactions of Syn-Ake, a synthetic peptide, with matrix metalloproteinases (MMPs) and Sirtuin 1 (SIRT1), which are the targets of anti-aging activities with in silico approaches, and to determine the antioxidant activity, and safety profile of the peptide by in vitro methods such as cytotoxicity (MTT) and genotoxicity (Ames) tests. The molecular docking study showed that the docking score energy of MMP receptors was in the order of MMP-13 < MMP-8 < MMP-1. Syn-Ake peptide provided the lowest and the most stable binding to the SIRT1 receptor at −9.32 kcal/mol. Binding interaction and protein-ligand stability of Syn-Ake with MMPs and SIRT1 in a dynamic system were predicted by 50 ns molecular dynamic (MD) simulation studies. The MD results showed that the Syn-Ake peptide remained stable in the active site of MMP-13 and SIRT1 receptors during 50 ns simulations. In addition, the antioxidant activity of Syn-Ake was investigated using diphenyl-2-picril-hydrazine (DPPH) method since it is crucial to remove free radicals that are effective in skin aging. The results revealed the concentration-dependent increased DPPH radical scavenging activity of the peptide. Finally, the safety of the Syn-Ake was investigated, and the safe dose of the peptide was determined. In conclusion, in silico and in vitro analyses show that the Syn-Ake peptide may hold promise in anti-aging formulations with its high efficacy and safety profile.

Communicated by Ramaswamy H. Sarma

Keywords:

• Syn-Ake
• molecular docking
• MD
• antioxidant
• toxicity

Acknowledgments

This work was supported by Yildiz Technical University Scientific Research Foundation [FCD-2021-4509]. In this study, the infrastructure of the Applied Nanotechnology and Antibody Production Laboratory established with TUBITAK support (project numbers: 115S132, 117S097 and 5200110) was used. The authors would also like to thank TUBITAK for their support. The authors are also very thankful to Schrödinger team for allowing using the docking and MD program with Schrödinger’s Small-Molecule Drug Discovery Suite and Desmond.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethical approval

In this research, no animals were used. There was no need for ethics approval.