Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, I-20133 Milano, Italy.
Department of Physics, Università di Cagliari, Citt. Universitaria, I-09042 Monserrato, Italy.
Nutrients. 2022 Apr 23;14(9):1775. doi: 10.3390/nu14091775.
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.
环（组氨酰-脯氨酰）（CHP）是一种环状二肽，具有良好的药代动力学性质和多种生物学活性。CHP 存在于许多富含蛋白质的食物和膳食补充剂中。虽然在生理 pH 值下稳定，但 CHP 可以打开生成两个对称的二肽（组氨酰-脯氨酰，脯氨酰-组氨酰），由于胃酸性环境，膳食 CHP 形成的二肽可能特别相关。尽管对非酶机制的研究甚少，但抗氧化和保护 CHP 的特性已被反复报道。尽管从未详细研究过 CHP 对α，β不饱和羰基的解毒活性，但由于其开放的二肽可能像已观察到的含组氨酸的二肽一样有效，因此本研究调查了 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，脯氨酰-组氨酸具有显著的活性，比 l-肉碱更具反应性。正如通过 DFT 计算研究的那样，增强的反应性可归因于所涉及的亚氨基中间体的更大亲电性。这些发现强调了伯胺（如 l-肉碱中所见）可以被具有有益的淬灭机制的仲胺取代。还评估了测试肽的血清稳定性，表明脯氨酰-组氨酸比 l-肉碱具有更大的稳定性。对接模拟表明，其水解可以被血清肉碱酶催化。总之，报告的结果表明，CHP 的抗氧化特性也可能归因于其开放二肽的解毒活性，这可能是 CHP 含量高的食物所引起的有益效果的原因。
