Polypyrrole-based Anion-Binding Agents

聚吡咯基阴离子结合剂

• 批准号: 6769607
• 负责人: Jonathan L Sessler
• 金额: $ 31.39万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6769607
• 关键词: anions; antineoplastics; biohazard detection; biomaterial development /preparation; biotechnology; bioterrorism /chemical warfare; chemical binding; chemical kinetics; chloride ion; drug design /synthesis /production; drug receptors; fluorescent dye /probe; fluoride ion; hydrogen ions; immunosuppressive; ion transport; nerve gas; optics; oxalates; phosphates; pyrroles; reagent /indicator; spectrometry; thermodynamics

DESCRIPTION (provided by applicant): This ongoing project involves the use of pyrrole NH hydrogen bonding interactions to bind, transport, and sense anions of biological relevance. It builds on an approach to anion recognition that was first put forward by the P.I. and his coworkers almost a decade ago and which has evolved to the point where it is now being adopted by an increasing number of academic laboratories world-wide. Meanwhile, pyrrole-based anion recognition events have been invoked recently to explain the mode of action of prodigiosin, a naturally occurring tripyrrolic entity with promising immunosuppressive and anticancer activity. Similar NH-anion interactions are implicated in pathways promoted by L-pyrrolysine, a new genetically encoded amino acid discovered earlier this year. Thus, the incentive to make and study pyrrole-based anion receptors is greater than ever. This is true both with regard to probing the basic determinants of anion binding and in terms of generating systems capable of targeting problems of medical and public health importance. These latter are represented by such diverse challenges as anionic metabolite sensing, chemical warfare agent detection, control of phosphate and oxalate concentrations in patients suffering from kidney failure, and multiple opportunities in drug development. Work to date has established that i) pyrrole-based receptors can bind and sense such physiologically important anions as phosphate, chloride, and oxalate, as well as fluoride, in polar media, ii) the strength and selectivity of the binding process can be fine-tuned through structural modifications, and iii) polymers containing pyrrolic receptors can be made. It has also led to the finding that several polypyrrole systems developed in the P.l.'s laboratory display cytotoxicities that meet or exceed those of prodigiosin. The proposed research will thus focus on using new and extant pyrrole-based receptors to i) probe more fully the kinetics and thermodynamics of anion recognition, ii) generate phosphate and oxalate binding materials for treating end-stage renal disease, iii) create supported sensors for detecting the hydrolysis products of organophosphate nerve gases, and iv) develop lead compounds that can be taken forward as potential new anti-cancer drugs and immunosuppressive agents.

描述（由申请人提供）：该正在进行的项目涉及使用吡咯 NH 氢键相互作用来结合、运输和感知生物相关的阴离子。它建立在 P.I. 首次提出的阴离子识别方法的基础上。和他的同事大约十年前，它已经发展到现在被世界各地越来越多的学术实验室采用的程度。 与此同时，基于吡咯的阴离子识别事件最近被用来解释灵菌红素的作用模式，灵菌红素是一种天然存在的三吡咯实体，具有良好的免疫抑制和抗癌活性。 L-吡咯赖氨酸促进的途径也涉及类似的 NH-阴离子相互作用，L-吡咯赖氨酸是今年早些时候发现的一种新的基因编码氨基酸。 因此，制造和研究基于吡咯的阴离子受体的动力比以往任何时候都大。 无论是在探索阴离子结合的基本决定因素方面，还是在生成能够解决重要的医学和公共卫生问题的系统方面，都是如此。 后者的特点是阴离子代谢物传感、化学战剂检测、肾衰竭患者磷酸盐和草酸盐浓度的控制以及药物开发的多种机会等各种挑战。 迄今为止的工作已经证实，i) 基于吡咯的受体可以在极性介质中结合和感知生理上重要的阴离子，如磷酸根、氯离子、草酸根以及氟化物，ii) 结合过程的强度和选择性可以很好-通过结构修饰进行调整，并且iii)可以制备含有吡咯受体的聚合物。 它还发现 P.L. 实验室开发的几种聚吡咯系统显示出的细胞毒性达到或超过了灵菌红的细胞毒性。 因此，拟议的研究将集中于使用新的和现有的基于吡咯的受体来i）更全面地探测阴离子识别的动力学和热力学，ii）生成用于治疗终末期肾病的磷酸盐和草酸盐结合材料，iii）创建支持的传感器用于检测有机磷酸盐神经气体的水解产物，以及 iv) 开发可作为潜在的新型抗癌药物和免疫抑制剂的先导化合物。