新型血管紧张素转换酶和二肽基肽酶抑制肽KALVAP的设计与实验验证。

IF 3.5 2区农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY

Journal of the Science of Food and Agriculture Pub Date : 2025-08-29 DOI:10.1002/jsfa.70156

Huan Wen, Jing Lan, Kuo Dang, Yanli Wang, Daodong Pan, Xinchang Gao, Yali Dang

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引用次数: 0

摘要

背景：KALVAP是一种从酸枣中提取的血管紧张素转换酶抑制剂，但对二肽基肽酶(DPP)-IV的抑制活性较差。为了弥补这一缺点，根据DPP-IV抑制肽的独特特征对KALVAP进行了修饰，得到了9个新的肽。体外和体内进一步验证了多肽对DPP-IV的抑制活性。结果：通过分子对接筛选后，WALVAP和WPLVAP的体外DPP-IV抑制活性分别比KALVAP（360.39±14.39 μmol L-1）高6.25倍和3.52倍。此外，WALVAP（201.88±8.27 μmol L-1）和WPLVAP（450.61±16.83 μmol L-1）对cco -2细胞的DPP-IV抑制活性优于KALVAP（1372.57±49.52 μmol L-1）。在体外和细胞实验的基础上，口服糖耐量试验表明，WALVAP和WPLVAP通过促进胰岛素（11.13±0.89%和11.61±0.44%）、GLP-1（11.12±0.89%和11.61±0.44%）和GIP（7.58±0.78%和7.66±0.11%）的分泌，显著改善C57BL/6小鼠的糖代谢。分子动力学模拟表明，WALVAP和WPLVAP主要通过Glu205、Trp629、Glu206、Arg125和Arg429抑制DPP-IV。结论：本次筛选出的新多肽WALVAP和WPLVAP均表现出良好的DPP-IV抑制活性。结果表明，该优化策略是可行的，可为药物设计提供参考。因此，WALVAP和WPLVAP可作为高血压和糖尿病患者的潜在候选药物。©2025化学工业协会。

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Design and experimental verification of novel angiotensin-converting enzyme and dipeptidyl peptidase IV inhibitory peptides from Ziziphus jujuba peptide KALVAP.

Background: KALVAP is an angiotensin-converting enzyme inhibitor derived from Ziziphus jujuba, but shows poor dipeptidyl peptidase (DPP)-IV inhibitory activity. To remedy this shortcoming, KALVAP was modified according to the distinctive features of DPP-IV inhibitory peptides, yielding nine novel peptides. The DPP-IV inhibitory activity of the peptides was further verified in vitro and in vivo.

Results: The in vitro DPP-IV inhibitory activities of WALVAP and WPLVAP were respectively 6.25- and 3.52-fold higher than that of KALVAP (360.39 ± 14.39 μmol L^-1) after screening through molecular docking. Moreover, WALVAP (201.88 ± 8.27 μmol L^-1) and WPLVAP (450.61 ± 16.83 μmol L^-1) displayed superior DPP-IV inhibitory activity to KALVAP (1372.57 ± 49.52 μmol L^-1) in Caco-2 cells. On the basis of in vitro and cellular experiments, oral glucose tolerance tests indicated that WALVAP and WPLVAP significantly improved glucose metabolism in C57BL/6 mice by promoting the secretion of insulin (11.13 ± 0.89% and 11.61 ± 0.44%), GLP-1 (11.12 ± 0.89% and 11.61 ± 0.44%) and GIP (7.58 ± 0.78% and 7.66 ± 0.11%). Molecular dynamics simulations revealed that WALVAP and WPLVAP mainly inhibited DPP-IV through Glu205, Trp629, Glu206, Arg125 and Arg429.

Conclusion: In summary, two new peptides, WALVAP and WPLVAP, were screened and exhibited excellent DPP-IV inhibitory activity. The results implied that the optimization strategy is feasible and can provide a reference for drug design. Thus WALVAP and WPLVAP could serve as potential drug candidates for patients with hypertension and diabetes mellitus. © 2025 Society of Chemical Industry.

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来源期刊

Journal of the Science of Food and Agriculture 工程技术-农业综合

CiteScore

8.10

自引率

4.90%

发文量

634

审稿时长

3.1 months

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