Laboratoire de Génie Enzymatique et de Microbiologie, Université de Sfax, Ecole Nationale d'Ingénieurs de Sfax, B.P. 1173-3038, Sfax, Tunisie.
J Proteomics. 2013 Oct 8;91:444-52. doi: 10.1016/j.jprot.2013.07.029. Epub 2013 Aug 3.
In recent years, food protein-derived bioactive peptides have received considerable attention because of their numerous health benefits. Amongst bioactive peptides, those with antihypertensive activity are receiving special attention due to their role in cardiovascular diseases. Goby protein hydrolysates (GPHs) prepared by treatment with five different crude bacterial proteases were found to exhibit varying degrees of angiotensin I-converting enzyme (ACE) inhibitory activity. The hydrolysate generated by the crude protease from Bacillus mojavensis A21, which displayed the highest ACE inhibitory activity, was further fractionated by size exclusion chromatography on a Sephadex G-25 and reversed-phase high performance liquid chromatography (RP-HPLC). The molecular masses and amino acid sequences of five peptides, in sub-fraction F5-2, which exhibited the highest ACE inhibitory activity, were determined using ESI-MS and ESI-MS/MS, respectively. The structures of these peptides were identified as Ala-Arg-Ser, Val-Val-Ala-Pro-Phe-Ala-His-Gly-Thr, Arg-Ser-Thr-Ala, Phe-Tyr-Pro-Pro, Arg-Cys-Ser-Ala-Gly-Val. Further, the sequences of fifteen peptides in the F5-4 sub-fraction, which exhibited high activity, were determined. Therefore, GPHs have a potential as hypotensive nutraceutical ingredients.
Peptides find many outlets of application in the biotechnological field, amongst which are pharmaceutical applications. Progression amongst new small molecules deposited like substance medicamentous blows itself. In this context, large pharmaceutical companies invest in peptide research to open therapeutic new prospects. Even if they are used as therapeutic agents for nearly one century in their natural form, the use of peptides remains parsimonious although we experienced a significant development since a few tens of years, in particular thanks to the clarification of the methods of production, chemical in solid or biological phase such as in phage display. Peptides present many advantages compared to traditional drugs that have small molecules, Generation of bioactive peptides by proteolysis of food proteins, using exogenous proteases, is a new and interesting approach for the production and identification of new and potent specific hypotensive agents. From another side, compared with natural peptides isolated from different sources, there is more diversity in structure and mode of action of the derived bioactive peptides. In fact, proteolysis of protein substrates, having different amino acid composition and sequences, by proteases having different specificities may generate numerous specific peptide inhibitors, with different lengths and amino acid sequences. These bioactive peptides have received considerable attention for their effectiveness in both the prevention and the treatment of hypertension.
近年来，由于其众多的健康益处，食物蛋白衍生的生物活性肽受到了相当大的关注。在生物活性肽中，具有降血压活性的肽因其在心血管疾病中的作用而受到特别关注。用五种不同的粗细菌蛋白酶处理制备的虾蛋白水解物（GPH）表现出不同程度的血管紧张素 I 转换酶（ACE）抑制活性。用来自莫哈韦沙漠芽孢杆菌 A21 的粗蛋白酶处理生成的水解物显示出最高的 ACE 抑制活性，进一步通过 Sephadex G-25 上的尺寸排阻色谱和反相高效液相色谱（RP-HPLC）进行分级。用 ESI-MS 和 ESI-MS/MS 分别确定在具有最高 ACE 抑制活性的亚级分 F5-2 中五个肽的分子质量和氨基酸序列。这些肽的结构被鉴定为 Ala-Arg-Ser、Val-Val-Ala-Pro-Phe-Ala-His-Gly-Thr、Arg-Ser-Thr-Ala、Phe-Tyr-Pro-Pro、Arg-Cys-Ser-Ala-Gly-Val。此外，确定了在具有高活性的 F5-4 亚级分中的十五个肽的序列。因此，GPH 具有作为降血压营养成分的潜力。
肽在生物技术领域有许多应用途径，其中包括药物应用。在新小分子作为物质药物沉积的推动下，进展不断。在这种情况下，大型制药公司投资于肽研究以开辟新的治疗前景。即使它们以天然形式作为治疗剂使用了近一个世纪，尽管我们在过去几十年中经历了显著的发展，特别是由于生产方法的阐明，例如在噬菌体展示中的固相或生物相的化学方法，肽的使用仍然很谨慎。与具有小分子的传统药物相比，肽具有许多优势，通过使用外源性蛋白酶对食物蛋白进行蛋白水解来生成生物活性肽，是生产和鉴定新的、有效的特异性降压剂的一种新的、有趣的方法。另一方面，与从不同来源分离的天然肽相比，衍生的生物活性肽在结构和作用方式上具有更多的多样性。事实上，通过具有不同特异性的蛋白酶对具有不同氨基酸组成和序列的蛋白质底物进行蛋白水解，可能会产生许多具有不同长度和氨基酸序列的特定肽抑制剂。这些生物活性肽因其在预防和治疗高血压方面的有效性而受到相当大的关注。
