金属离子可调控的PAT识别及DNA嵌入双靶向"多胺-药物"缀合物的设计、合成及抗肿瘤活性

项目名称： 金属离子可调控的PAT识别及DNA嵌入双靶向"多胺-药物"缀合物的设计、合成及抗肿瘤活性

项目编号： No.21302041

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 罗稳

作者单位： 河南大学

项目金额： 25万元

中文摘要： 多胺（polyamines）是一类具有广泛生理活性的生物内源性小分子，在抗肿瘤药物设计中颇受关注，然而其缀合物的研究报道较少。虽然本课题组曾利用肿瘤细胞通过多胺转运蛋白（PAT）摄取更多的多胺这一特性进行"多胺-药物"缀合物的设计，然而如何精确地对PAT调控来设计有"开-关"效应的多胺缀合物，仍具有巨大挑战性。本项目基于PAT转运及多胺循环机制，选择平面稠环类DNA嵌入剂为研究对象，通过金属离子调控PAT，深入地研究PAT转运机理、分子识别、多胺循环、DNA嵌入以及抗肿瘤等分子机制，并以PAT及DNA为双靶点设计"多胺-药物"缀合物，不但有可能发现新的候选药物，而且能够为推进PAT分子结构与转运机制的理论研究提供一种新思路。

中文关键词： 药物合成；多胺；抗肿瘤；金属调控；胆碱酯酶

英文摘要： Polyamines is one of remarkable endogenous small molecule with widely biological activity which arouses people's attention in the design of anticancer drugs. However, there is few research reported. Although our group have designed "polyamines-drug" conjugates by utilizing tumor cells uptaking more polyamine through the polyamine transporter (PAT), however, how to design polyamine conjugates precisely by PAT regulation "open-off" effects, is still a huge challenge. This project is based on the PAT transporters and polyamine cycle mechanism, choosing DNA intercalating agents as the research object, by utilizing of PAT regulation, metal ions, PAT transport, molecular recognition, polyamine cycle, DNA intercalating mechanism as well as anti-tumor mechanism to design "polyamines-Drug" conjugates, not only to find for new anti-tumor drug candidates, but also to provide new ideas for advancing PAT molecular structure and transport mechanism.

英文关键词： drug synthesis；polyamine；anti-tumor；metal-controlled；cholinesterase