Abstract：
This study aimed to screen for a novel osteogenic peptide based on the calcium-sensing receptor (CaSR) and explore its molecular mechanism and gastrointestinal stability. In this study, a novel osteogenic peptide (Phe-Ser-Gly-Leu, FSGL) derived from bovine bone collagen hydrolysate was successfully screened by molecular docking and synthesised by solid phase peptide synthesis for further analysis. Cell experiments showed that FSGL significantly enhanced the osteogenic activity of MC3T3-E1 cells by acting on CaSR, including proliferation (152.53%), differentiation, and mineralization. Molecular docking and molecular dynamics further demonstrated that FSGL was a potential allosteric activator of CaSR, that turned on the activation switch of CaSR by closing the Venus flytrap (VFT) domain and driving the two protein chains in the VFT domain to easily form dimers. In addition, 96.03% of the novel osteogenic peptide FSGL was stable during gastrointestinal digestion. Therefore, FSGL showed substantial potential for enhancing the osteogenic activity of osteoblasts. This study provided new insights for the application of CaSR in the targeted screening of osteogenic peptides to improve bone health.
摘要：
本研究旨在筛选一种基于钙敏感受体(CaSR)的新型成骨肽,并探讨其分子机制和胃肠道稳定性。在这项研究中,一种新型成骨肽（Phe-Ser-Gly-Leu，通过分子对接成功筛选了来自牛骨胶原水解物的FSGL），并通过固相肽合成合成进行了进一步分析。细胞实验表明,FSGL通过作用于CaSR,显著增强MC3T3-E1细胞的成骨活性,包括增殖（152.53%），分化,和矿化。分子对接和分子动力学进一步证明FSGL是CaSR潜在的变构激活剂,通过关闭金星捕蝇（VFT）域并驱动VFT域中的两个蛋白质链轻松形成二聚体来打开CaSR的激活开关。此外,96.03%的新型成骨肽FSGL在胃肠消化过程中稳定。因此,FSGL显示出增强成骨细胞成骨活性的巨大潜力。本研究为CaSR在靶向筛选成骨肽以改善骨健康方面的应用提供了新的见解。
