Biodynamical Implications of Grafting Position Alteration in Engineered Mimics of Parkinson's Inhibitor MCoCP4

N. Ilieva, E. Lilkova, P. Petkov, Xubiao Peng, Yadi Cheng
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Abstract

Proteins are currently the fastest-growing class of new therapeutic compounds but smaller proteins and peptides are generally not suitable for use as drugs. Using cyclotides – special knotted proteins stabilized by three pairs of disulphide bonds – as a transport means by grafting onto them as a scaffolding the bioactive peptides can enhance their stability, cellular uptake, and overall efficacy. Experimental methods for creating peptide aptamers are highly time- and resources-consuming. In silico approaches may speed up this process by pre-selecting the drug candidates based on certain biodynamic criteria. In this study, we probe the hypothesis about a relation between the scaffolding conformational stability in conjunction with certain plasticity upon grafting of functionally important domains and the desired biological activity of the modified through the grafting process molecules.
帕金森抑制剂 MCoCP4 工程模拟物中接枝位置改变的生物动力学影响
蛋白质是目前增长最快的一类新治疗化合物,但较小的蛋白质和肽通常不适合用作药物。利用环肽(由三对二硫键稳定的特殊结蛋白)作为运输手段,将生物活性肽嫁接到环肽上作为支架,可以提高其稳定性、细胞吸收率和整体疗效。制造多肽适配体的实验方法非常耗费时间和资源。硅学方法可以根据某些生物动力学标准预选候选药物,从而加快这一过程。在本研究中,我们探讨了支架构象稳定性与功能性重要结构域嫁接后的可塑性之间的关系,以及通过嫁接过程修饰的分子所需的生物活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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