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从菜豆水解产物中鉴定新型生物活性肽的抗氧化、抗增殖、蛋白糖化抑制作用及其分子对接研究

Identification, protein antiglycation, antioxidant, antiproliferative, and molecular docking of novel bioactive peptides produced from hydrolysis of Lens culinaris.

机构信息

Department of Biochemistry, Faculty of Science, King Abdulaziz University (KAU), Jeddah, Saudi Arabia.

Bioactive Natural Products Research Group, King Abdulaziz University (KAU), Jeddah, Saudi Arabia.

出版信息

J Food Biochem. 2020 Dec;44(12):e13494. doi: 10.1111/jfbc.13494. Epub 2020 Oct 4.

DOI:10.1111/jfbc.13494
PMID:33015836
Abstract

Bioactive peptides produced from natural sources are considered as strategic target for drug discovery. Hyperglycemia caused protein glycation alters the structure of many tissues that impairs their functions and lead complications diseases in human body. This study investigated the bioactive peptides produced from red and brown Lens culinaris that might inhibit protein glycation to prevent diabetic complications. In this study, red and brown Lens culinaris protein hydrolysates were prepared by tryptic digestion, using an enzyme/substrate ratio of 1:20 (g/g), at 37°C, 12 hr then peptide fractions <3 kDa were filtered by using ultrafiltration membranes. Protective ability against protein glycation, DPPH radical scavenging, and anti-proliferative activities (on HepG2, MCF-7, and PC3 cell lines) of peptide fractions were assayed in vitro. Results showed that glycation was inhibited by peptides from 28.1% to 68.3% in different test model. PC3 cell line was more sensitive to the peptides which showed strong anticancer activity with lower IC50 (0.96 mg/ml). Peptide fractions were sequenced by HPLC-MS-MS. Twenty eight novel peptides sequences was identified. In silico study, two peptides could be developed as a potential bioactive peptides exhibited antiglycation, antioxidant, and antiproliferative activities. PRACTICAL APPLICATIONS: Peptides are becoming an emerging source of medications with the development of new technologies. We have selected Lens Culinaris as one of the rich sources of proteins to explore novel bioactive peptides encapsulated in its seeds. Peptides fractions demonstrated protective ability against protein glycation, strong antioxidant potential, and promising antiproliferative activity. We have identified 28 novel peptides and molecular docking study revealed that some peptides showed strong binding potential to insulin receptor and ACE. Thus, these peptides might be used to manage diabetes complication as well as COVID-19 disease due to their interaction with ACE. However, those peptides needs to be further studied as a potential new drug.

摘要

从天然来源中产生的生物活性肽被认为是药物发现的战略目标。高血糖引起的蛋白质糖化会改变许多组织的结构,从而损害它们的功能,并导致人体并发症疾病。本研究调查了来自红棕色 Lens culinaris 的生物活性肽,这些肽可能抑制蛋白质糖化,以预防糖尿病并发症。在这项研究中,通过胰蛋白酶消化制备了红棕色 Lens culinaris 蛋白水解物,使用酶/底物比为 1:20(g/g),在 37°C 下孵育 12 小时,然后用超滤膜过滤<3 kDa 的肽段。体外测定肽段对蛋白质糖化的保护能力、DPPH 自由基清除能力和抗增殖活性(在 HepG2、MCF-7 和 PC3 细胞系上)。结果表明,在不同的测试模型中,肽对糖化的抑制率为 28.1%至 68.3%。PC3 细胞系对肽更敏感,表现出强烈的抗癌活性,IC50 较低(0.96mg/ml)。肽段通过 HPLC-MS-MS 进行测序。鉴定出 28 种新的肽序列。计算机研究表明,两种肽可以开发为具有抗糖化、抗氧化和抗增殖活性的潜在生物活性肽。实际应用:随着新技术的发展,肽类正在成为一种新兴的药物来源。我们选择 Lens Culinaris 作为富含蛋白质的来源之一,以探索其种子中包裹的新型生物活性肽。肽段显示出对蛋白质糖化的保护能力、强大的抗氧化潜力和有前途的抗增殖活性。我们已经鉴定出 28 种新的肽,分子对接研究表明,一些肽与胰岛素受体和 ACE 具有很强的结合潜力。因此,由于它们与 ACE 的相互作用,这些肽可能被用于治疗糖尿病并发症以及 COVID-19 疾病。然而,这些肽还需要进一步研究,作为一种潜在的新药。

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