人血清中二肽基肽酶-4的部分纯化及某些腈衍生物对其抑制作用的研究

Firas Shawqi Algburi, Nadia Y Al-Tikrity, H. Ulusal, T. Taşkın-Tok, Omeed Akbar Ali
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摘要

该研究包括从人的天然血清中部分纯化二肽基肽酶-4(Dpp-4)。酶的纯化分为三步,硫酸铵(50%)沉淀,透析和Sephadex G-100凝胶过滤。结果表明,纯化后的Dpp-4活性和比活性显著升高,总活性降低。分离柱上活性最高的纯化酶的下降与活性最高的蛋白的下降相同。研究了纯化酶所使用的腈衍生物的抑制活性。利用丁腈衍生物抑制Dpp-4的活性,根据衍生物与降血糖药物(Dpp-4抑制剂类型)有效基团位点的相似性选择。结果表明,两种腈衍生物在不同浓度下均有抑制作用。这些抑制剂可以降低糖尿病患者的血糖水平。此外,在实验过程的基础上,进行分子对接,在原子水平上了解化合物与Dpp-4的相互作用机理。
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Partial Purification of Dipeptidyl Peptidase-4 From Human Blood Serum and Study the Inhibitory Effect of Some Nitrile Derivatives on it
The research includes the partial purification of dipeptidyl peptidase-4(Dpp-4) from a person’s natural serum.The enzyme was purified in three steps, precipitation by ammonium sulfate (50%), dialysis and gel filtration by Sephadex G-100. The results showed a significant increase of Dpp-4 activity and specific activity,and a decrease in total activity after purification.The descent of the purified enzyme with the highest activity from the separation column was identical to the descending of the protein with the highest activity. The inhibitory activity of nitrile derivatives that were used on the purified enzyme was studied. Nitrile derivatives were used to inhibit the activity of the Dpp-4, selected based on similarity in sites of effective groups between derivatives and anti-hyperglycemic drugs (Dpp-4 inhibitors type). The results show an inhibitory effect by the two nitrile derivatives with different concentrations.These inhibitors can work to reduce the level of blood sugar in people with diabetes. Moreover,Molecular docking was exerted to understand interaction mechanism of the compounds against Dpp-4 at atomic level based on experimental processes.
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