Abstract：
Calixarenes are displaying great potential for the development of new drug delivery systems, diagnostic imaging, biosensing devices and inhibitors of biological processes. In particular, calixarene derivatives are able to interact with many different enzymes and function as inhibitors. By screening of the potential drug target database (PDTD) with a reverse docking procedure, we identify and discuss a selection of 100 proteins that interact strongly with calix[4]arene. We also discover that leucine (23.5 %), isoleucine (11.3 %), phenylalanines (11.3 %) and valine (9.5 %) are the most frequent binding residues followed by hydrophobic cysteines and methionines and aromatic histidines, tyrosines and tryptophanes. Top binders are peroxisome proliferator-activated receptors that already are targeted by commercial drugs, demonstrating the practical interest in calix[4]arene. Nuclear receptors, potassium channel, several carrier proteins, a variety of cancer-related proteins and viral proteins are prominent in the list. It is concluded that calix[4]arene, which is characterized by facile access, well-defined conformational characteristics, and ease of functionalization at both the lower and higher rims, could be a potential lead compound for the development of enzyme inhibitors and theranostic platforms.
摘要：
杯芳烃在开发新的药物递送系统方面显示出巨大的潜力，诊断成像,生物传感装置和生物过程抑制剂。特别是,杯芳烃衍生物能够与许多不同的酶相互作用并充当抑制剂。通过反向对接程序筛选潜在的药物靶标数据库（PDTD），我们鉴定并讨论了100种与杯[4]芳烃强烈相互作用的蛋白质。我们还发现亮氨酸(23.5%)，异亮氨酸（11.3%），苯丙氨酸（11.3％）和缬氨酸（9.5％）是最常见的结合残基，其次是疏水性半胱氨酸和甲硫氨酸和芳族组氨酸，酪氨酸和色氨酸。主要的结合剂是过氧化物酶体增殖物激活的受体，已经被商业药物靶向，证明对杯[4]芳烃的实际兴趣。核受体,钾通道，几种载体蛋白，多种癌症相关蛋白和病毒蛋白在列表中突出。结论是卡利克斯[4]芳烃，其特点是访问方便，定义明确的构象特征，并且易于在较低和较高的轮辋上功能化，可能是开发酶抑制剂和治疗平台的潜在先导化合物。
