合理的序列修饰将食物来源的肽升级为更强的α-葡萄糖苷酶活性和胰岛素抵抗的双重功能调节因子
Rational Sequence Modification Upgrades a Food-Derived Peptide into a Stronger Dual-Functional Regulator of α-Glucosidase Activity and Insulin Resistance.
摘要(中文译文)
抑制α-葡萄糖苷酶和改善胰岛素抵抗（IR）是治疗2型糖尿病（T2DM）的关键策略。我们前期工作获得了一种新型α-葡萄糖苷酶抑制肽FAPSW，然而其活性弱于阿卡波糖。为进一步增强其活性，以FAPSW为模板，通过氨基酸替换构建了17种新型肽。其中，YAPSW（IC = 0.126 ± 0.008 mM）表现出比FAPSW和阿卡波糖更强的α-葡萄糖苷酶抑制作用。分子对接表明，氢键并非肽介导α-葡萄糖苷酶抑制的唯一决定因素，而分子动力学模拟揭示YAPSW抑制活性增强主要源于其与3A4A更稳定的结合。此外，FAPSW和YAPSW均可改善IR，且YAPSW对IRS-1/PI3K/AKT信号通路的作用强于FAPSW。本研究为优化α-葡萄糖苷酶抑制肽提供了思路，并支持YAPSW作为多功能食品配料用于T2DM管理的潜在应用。
Abstract
Inhibition of α-glucosidase and improvement of insulin resistance (IR) are key strategies for treating type 2 diabetes mellitus (T2DM). Our previous work obtained a novel α-glucosidase inhibitory peptide, FAPSW. However, its activity was weaker than acarbose. To further enhance its activities, 17 novel peptides were constructed by amino acid substitution using FAPSW as a template. Among them, YAPSW (IC = 0.126 ± 0.008 mM) exhibited stronger α-glucosidase inhibition than FAPSW and acarbose. Molecular docking suggested that hydrogen bonds were not the sole determinants of peptide-mediated α-glucosidase inhibition, while molecular dynamics simulations revealed that the enhanced inhibitory activity of YAPSW primarily resulted from its more stable binding to 3A4A. Moreover, FAPSW and YAPSW could improve IR and YAPSW exhibited stronger effects on IRS-1/PI3K/AKT signaling pathway than FAPSW. This study provides insights into optimizing α-glucosidase inhibitory peptides and supports the potential application of YAPSW as a multifunctional food ingredient for T2DM management.
如何引用
AMA
Xiang Wang, Yejun Deng, Junhao Wan, Caihong Zhang, Yong Liu, Yuechao Zhang, et al. Rational Sequence Modification Upgrades a Food-Derived Peptide into a Stronger Dual-Functional Regulator of α-Glucosidase Activity and Insulin Resistance.. Journal of agricultural and food chemistry. 2026; doi:10.1021/acs.jafc.6c01142.
APA
Xiang Wang, Yejun Deng, Junhao Wan, Caihong Zhang, Yong Liu, Yuechao Zhang, et al (2026). Rational Sequence Modification Upgrades a Food-Derived Peptide into a Stronger Dual-Functional Regulator of α-Glucosidase Activity and Insulin Resistance.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.6c01142
GB/T 7714
Xiang Wang, Yejun Deng, Junhao Wan, Caihong Zhang, Yong Liu, Yuechao Zhang, et al. Rational Sequence Modification Upgrades a Food-Derived Peptide into a Stronger Dual-Functional Regulator of α-Glucosidase Activity and Insulin Resistance.[J]. Journal of agricultural and food chemistry, 2026 doi:10.1021/acs.jafc.6c01142.
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