POLYPYRROLE BASED ANION RECEPTORS

这个项目的目标是解决长期存在的毒品问题 送货。具体地说，这个项目关注的是提供 现代抗病毒化疗的辅助剂，设计的受体能够 通过不同的疏水膜运输核苷酸类似物 障碍。这样的运输代理，凭借扩大可用的 阿森纳可用的抗病毒药物，可以在 增强我们治疗疱疹等令人衰弱的疾病的能力， 肝炎、麻疹和艾滋病。与上述有关，并作为一个附属的 项目目标，是制备选择性受体和载体 对于氯离子。这些，通过可能允许临床上的 调节上皮细胞氯离子外流的增加，可能 为分子水平的治疗提供了新的重要武器 囊性纤维化。 先前的工作导致了两种特定核酸碱基的发展 识别单元和一种新的基于 质子化的膨胀的卟啉的使用。目前的项目将建立 并提供用于核苷酸运输的载体系统，该载体系统 在中性pH和核酸碱基特定的情况下都有效。这 将通过制备包含这两种受体的重复受体，如1 用于磷酸盐结合和嘌呤/嘧啶的扩展的卟啉基团 “附属物”，用于识别特定的核酸碱基。跟随 适当的背景工作，其中关键的机械特征 扩展的卟啉与阴离子(包括氯化物)的相互作用是 这些系统和其他有希望的系统将作为推定的系统进行测试 核苷酸类似物运输剂。这将首先使用 对膜系统进行建模，然后使用感染病毒的细胞系。从… 这些研究的结果和标准的急性毒性测试的结果， 将评估佐剂疗效。然后，这种功效将反过来， 根据受体结构进行分析，并用作基础 制备尚未改进的识别剂和运输剂。就这样， 提出了一套临床上可行的抗病毒药物载体 交付可以作为本NIH赞助的结果 研究。还建议采用类似的设计顺序， 合成、测试和分析可用于开发扩展 能够影响临床调节的卟啉类载体 细胞氯离子浓度。在这种情况下，必需的 系统将不需要核酸碱基附件，因此应该 准备和测试要容易得多。

The goal of this project is to solve a long-standing problem in drug delivery. Specifically, this project is concerned with providing adjuvants for modern antiviral chemotherapy, designed receptors capable of transporting nucleotide analogues through various hydrophobic membrane barriers. Such transport agents, by virtue of expanding the available arsenal of useable antiviral agents, could play an important role in augmenting our ability to treat such debilitating diseases as herpes, hepatitis, measles, and AIDS. Related to the above, and ancillary as a project objective, is the preparation of selective receptors and carriers for chloride anion. These, by possibly allowing for a clinically regulated increase in epithelial cell chloride anion egress, could provide a new and important weapon for the molecular level treatment of cystic fibrosis. Prior work has led to the development of both specific nucleic acid base recognition units and a new approach to phosphate binding based on the use of protonated expanded porphyrins. The present project will build on this work and provide carrier systems for nucleotide transport that are both effective at neutral pH and nucleic acid base specific. This will be done by preparing ditopic receptors, such as 1, that contain both expanded porphyrin moieties for phosphate binding and purine/pyrimidine "appendages" for specific nucleic acid base recognition. Following appropriate background work, in which the key mechanistic features of expanded porphyrin-to-anion interactions (including chloride) are defined, these and other promising systems will be tested as putative nucleotide analogue transport agents. This will be done first using model membrane systems and then using virus-infected cell lines. From the results of these studies and those of standard acute toxicity tests, adjuvant efficacy will be assessed. This efficacy will then, in turn, be analyzed in terms of receptor structure and used as the basis for preparing yet-improved recognition and transport agents. In this way, it is proposed, a clinically viable set of carriers for antiviral drug delivery can be produced as the result of the present NIH-sponsored research. It is also proposed that a similar sequence of design, synthesis, testing, and analysis can be used to develop expanded porphyrin based carriers capable of effecting clinical regulation of cellular chloride anion concentration. In this case, the requisite system will not require a nucleic acid base appendage and should hence be much easier to prepare and test.