Therapeutic Potential of Foldamers: From Chemical Biology Tools To Drug Candidates?
Therapeutic Potential of Foldamers: From Chemical Biology Tools To Drug Candidates?
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DOI：
10.1021/acs.jmedchem.6b00376
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发表时间：
2016-11-10
影响因子：
7.3
通讯作者：
Valeur, Eric
中科院分区：
文献类型：
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作者：
Gopalakrishnan, Ranganath;Frolov, Andrey I.;Valeur, Eric
在过去的十年里，折叠分子逐渐成为模仿蛋白质二级结构的有用结构。从治疗的角度来看，由各种氨基酸骨架组成的多肽类Folamers一直是研究最多的，而多芳香族Folamers几乎没有从其鼻腔进化而来，由于其较差的类药物性质，仍然困扰着药物化学家。尽管有这些限制，但这门复合课仍可能提供学习具有挑战性的目标或提供化学生物学工具的机会。Folamer候选药物进入临床的潜力仍然很大。然而，该领域的进步已经证明了它们发现下一代疗法的潜力。从这一角度出发，在药物发现的背景下回顾了目前关于叶黄素的知识。讨论了药物发现的早期阶段的最新进展，包括命中发现、靶点验证、优化和分子建模。此外，还对挑战和重点领域进行了辩论，并突出了差距。
Over the past decade, foldamers have progressively emerged as useful architectures to mimic secondary structures of proteins. Peptidic foldamers, consisting of various amino acid based backbones, have been the most studied from a therapeutic perspective, while polyaromatic foldamers have barely evolved from their nascency and remain perplexing for medicinal chemists due to their poor drug-like nature. Despite these limitations, this compound class may still offer opportunities to study challenging targets or provide chemical biology tools. The potential of foldamer drug candidates reaching the clinic is still a stretch. Nevertheless, advances in the field have demonstrated their potential for the discovery of next generation therapeutics. In this perspective, the current knowledge of foldamers is reviewed in a drug discovery context. Recent advances in the early phases of drug discovery including hit finding, target validation, and optimization and molecular modeling are discussed. In addition, challenges and focus areas are debated and gaps highlighted.