Graduate School of Natural and Applied Science, Yildiz Technical University, Istanbul, Turkey.
Faculty of Chemical and Metallurgical Engineering, Department of Bioengineering, Yildiz Technical University, Istanbul, Turkey.
J Biomol Struct Dyn. 2024 Jul;42(10):5015-5029. doi: 10.1080/07391102.2023.2223681. Epub 2023 Jun 22.
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 approaches, and to determine the antioxidant activity, and safety profile of the peptide by 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, and 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.
全球人口老龄化的增加促使科学家们转向研究以防止衰老过程。在这种情况下，合成肽作为开发新的抗衰老产品的候选分子出现。本研究旨在通过分子对接和分子动力学（MD）模拟研究来研究合成肽 Syn-Ake 与基质金属蛋白酶（MMPs）和 Sirtuin 1（SIRT1）的可能相互作用，SIRT1 是抗衰老活性的靶标，并通过细胞毒性（MTT）和遗传毒性（Ames）试验等方法确定该肽的抗氧化活性和安全性特征。分子对接研究表明，MMP 受体的对接评分能量顺序为 MMP-13 <MMP-8 <MMP-1。Syn-Ake 肽与 SIRT1 受体的结合最低且最稳定，结合能为-9.32 kcal/mol。通过 50 ns 分子动力学（MD）模拟研究预测了 Syn-Ake 肽与 MMPs 和 SIRT1 的结合相互作用和蛋白质-配体在动态系统中的稳定性。MD 结果表明，在 50 ns 模拟过程中，Syn-Ake 肽在 MMP-13 和 SIRT1 受体的活性部位保持稳定。此外，还使用二苯基-2-苦基肼（DPPH）法研究了 Syn-Ake 的抗氧化活性，因为它对于去除自由基是至关重要的，自由基在皮肤衰老中是有效的。结果表明，该肽具有浓度依赖性的 DPPH 自由基清除活性。最后，研究了 Syn-Ake 的安全性，并确定了该肽的安全剂量。总之，分子对接和分子动力学模拟分析表明，Syn-Ake 肽可能因其高效和安全的特性而在抗衰老配方中具有潜力。
