School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China; Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center, Guangzhou 510650, China.
Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, 3210 N. Cramer St., Milwaukee, WI 53211, United States.
Food Chem. 2024 Dec 15;461:140838. doi: 10.1016/j.foodchem.2024.140838. Epub 2024 Aug 10.
Milk casein is regarded as source to release potential sleep-enhancing peptides. Although various casein hydrolysates exhibited sleep-enhancing activity, the underlying reason remains unclear. This study firstly revealed the structural features of potential sleep-enhancing peptides from casein hydrolysates analyzed through peptidomics and multivariate analysis. Additionally, a random forest model and a potential Tyr-based peptide library were established, and then those peptides were quantified to facilitate rapidly-screening. Our findings indicated that YP-, YI/L, and YQ-type peptides with 4-10 amino acids contributed more to higher sleep-enhancing activity of casein hydrolysates, due to their crucial structural features and abundant numbers. Furthermore, three novel strong sleep-enhancing peptides, YQKFPQY, YPFPGPIPN, and YIPIQY were screened, and their activities were validated in vivo. Molecular docking results elucidated the importance of the YP/I/L/Q- structure at the N-terminus of casein peptides in forming crucial hydrogen bond and π-alkyl interactions with His-102 and Asn-60, respectively in the GABA receptor for activation.
牛奶酪蛋白被认为是释放潜在助眠肽的来源。虽然各种酪蛋白水解物都表现出助眠活性，但潜在的原因尚不清楚。本研究首次通过肽组学和多变量分析揭示了酪蛋白水解物中潜在助眠肽的结构特征。此外，建立了随机森林模型和潜在的 Tyr 基肽库，然后对这些肽进行定量，以方便快速筛选。我们的研究结果表明，具有 4-10 个氨基酸的 YP-、YI/L-和 YQ-型肽由于其关键的结构特征和丰富的数量，对酪蛋白水解物更高的助眠活性贡献更大。此外，筛选出三个新的强睡眠增强肽 YQKFPQY、YPFPGPIPN 和 YIPIQY，并在体内验证了它们的活性。分子对接结果阐明了酪蛋白肽 N 末端 YP/I/L/Q-结构在与 GABA 受体形成关键氢键以及与 His-102 和 Asn-60 形成π-烷基相互作用中的重要性，从而激活 GABA 受体。
