Cyclo(His-Pro) 通过其开放的含组氨酸二肽发挥保护性羰基猝灭作用,Nutrients

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Cyclo(His-Pro) 通过其开放的含组氨酸二肽发挥保护性羰基猝灭作用
Nutrients ( IF 4.546 ) Pub Date : 2022-04-23 , DOI: 10.3390/nu14091775
Luca Regazzoni ₁ , Laura Fumagalli ₁ , Angelica Artasensi ₁ , Silvia Gervasoni _{1,

2} , Ettore Gilardoni ₁ , Angelica Mazzolari ₁ , Giancarlo Aldini ₁ , Giulio Vistoli ₁

Affiliation

Cyclo(His-Pro) (CHP) 是一种环状二肽，具有良好的药代动力学特性和多种生物活性。CHP 存在于许多富含蛋白质的食品和膳食补充剂中。虽然在生理 pH 下稳定，CHP 可以打开产生两种对称二肽（His-Pro、Pro-His），由于胃酸性环境，其形成可能与膳食 CHP 特别相关。尽管对非酶机制的研究很少，但其抗氧化和保护性 CHP 特性已被多次报道。CHP 对 α,β 不饱和羰基的解毒活性从未被详细研究过，尽管其开放二肽可能是有效的，正如已经在含组氨酸的二肽中观察到的那样。因此，本研究研究了 TRH、CHP 及其开放衍生物对 4-羟基-2-壬烯醛的清除特性。所得结果表明Pro-His具有显着的活性并且比L-肌肽更具反应性。根据 DFT 计算的研究，反应活性的增强可归因于所涉及的亚胺中间体具有更大的亲电子性。这些发现强调伯胺（如L-肌肽）可以被仲胺取代，对猝灭机制具有有益的影响。还评估了测试肽的血清稳定性，结果表明 Pro-His 的特点是比L-肌肽具有更高的稳定性。对接模拟表明其水解可以被血清肌肽酶催化。总而言之，报告的结果证明，CHP 的抗氧化特性也可能是由于其开放二肽的解毒活性，这可能是含有 CHP 的食物引起的有益作用的原因。

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Cyclo(His-Pro) Exerts Protective Carbonyl Quenching Effects through Its Open Histidine Containing Dipeptides

Cyclo(His-Pro) (CHP) is a cyclic dipeptide which is endowed with favorable pharmacokinetic properties combined with a variety of biological activities. CHP is found in a number of protein-rich foods and dietary supplements. While being stable at physiological pH, CHP can open yielding two symmetric dipeptides (His-Pro, Pro-His), the formation of which might be particularly relevant from dietary CHP due to the gastric acidic environment. The antioxidant and protective CHP properties were repeatedly reported although the non-enzymatic mechanisms were scantly investigated. The CHP detoxifying activity towards α,β unsaturated carbonyls was never investigated in detail, although its open dipeptides might be effective as already observed for histidine containing dipeptides. Hence, this study investigated the scavenging properties of TRH, CHP and its open derivatives towards 4-hydroxy-2-nonenal. The obtained results revealed that Pro-His possesses a marked activity and is more reactive than l-carnosine. As investigated by DFT calculations, the enhanced reactivity can be ascribed to the greater electrophilicity of the involved iminium intermediate. These findings emphasize that the primary amine (as seen in l-carnosine) can be replaced by secondary amines with beneficial effects on the quenching mechanisms. Serum stability of the tested peptides was also evaluated, showing that Pro-His is characterized by a greater stability than l-carnosine. Docking simulations suggested that its hydrolysis can be catalyzed by serum carnosinase. Altogether, the reported results evidence that the antioxidant CHP properties can be also due to the detoxifying activity of its open dipeptides, which might be thus responsible for the beneficial effects induced by CHP containing food.

更新日期：2022-04-25

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