生物物理模型表明,omega-3多不饱和脂肪酸乙酯对促炎花生四烯酸级联酶具有很高的亲和力

Q3 Medicine
I. Torshin, O. Gromova
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引用次数: 0

摘要

背景。ω-3多不饱和脂肪酸(ω-3 PUFAs)在现代心脏病学中被广泛应用。二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)的抗炎作用主要是通过调节花生四烯酸(ARA)级联的活性来实现的。目的:对多种形式PUFAs (ARA、EPA、DHA、EPA和DHA乙酯)与ARA级联的三种靶蛋白酶(环氧化酶-1 (COX-1)、cox - 2,5 -脂氧化酶(5-LPOG))的相互作用进行生物物理分析。材料和方法。利用ECMMS包计算了相对于受体袋不同初始位置的配体-受体复合物的最小能量和蛋白质的分子能量谱(从溶剂到蛋白质的侧链转移的能量)。EPA和DHA乙酯的特征是目标蛋白的比结合能的绝对值明显高于ARA或单纯的EPA/DHA。例如,在COX-2的情况下,EPA、DHA和EPA乙酯具有相似的∆G值(-3.0…-3.1 kcal/mol),而COX-2与DHA乙酯的配合物更为稳定(∆G = -3.4 kcal/mol)。以5-LPOG酶为例,与EPA乙酯的配合物最稳定(∆∆G = -1.62 kcal/mol)。较高的绝对结合能表明EPA和DHA乙酯对ARA级联酶具有较高的亲和力。结果表明,EPA和DHA乙酯对ARA级联酶的高亲和力是ω-3 PUFAs具有高度标准化疗效的分子基础之一。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Biophysical modeling indicates a high affinity of ethyl esters of omega-3 polyunsaturated fatty acids to the enzymes of the pro-inflammatory arachidonic acid cascade
Background. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are widely used in modern cardiology. The anti-inflammatory effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is realized, in particular, by modulating the activity of the arachidonic acid (ARA) cascade.Objective: to conduct biophysical analysis of the interactions of various forms of PUFAs (ARA, EPA, DHA, EPA and DHA ethyl esters) with three target proteins-enzymes of the ARA cascade (cyclooxygenase-1 (COX-1), COX-2, 5-lipoxygenase (5-LPOG)).Material and methods. The minimization of the energy of the ligand-receptor complexes at various initial positions of the molecule relative to the receptor pocket and the molecular energy profiles of the protein (the energy of side chain transfer from solvent to protein) were calculated using the ECMMS package.Results. EPA and DHA ethyl esters were characterized by significantly higher absolute values of specific binding energies of target proteins than ARA or simply EPA/DHA. For example, in the case of COX-2, EPA, DHA and EPA ethyl ester had similar ∆∆G values (–3.0...–3.1 kcal/mol), while the COX-2 complex with DHA ethyl ester was somewhat more stable (∆∆G = –3.4 kcal/mol). In the case of the 5-LPOG enzyme, the complex with EPA ethyl ester was the most stable (∆∆G = –1.62 kcal/mol). Higher absolute binding energies indicate a higher affinity of EPA and DHA ethyl esters to enzymes of the ARA cascade.Conclusion. The results suggest that the high affinity of EPA and DHA ethyl esters to the enzymes of the ARA cascade is one of the molecular bases of therapeutic efficacy of ω-3 PUFAs with high degree of standardization.
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来源期刊
Farmakoekonomika
Farmakoekonomika Medicine-Health Policy
CiteScore
1.70
自引率
0.00%
发文量
43
审稿时长
8 weeks
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