CELL TRANSPORT OF PHOSPHATES AND OLIGONUCLEOTIDES

描述：（改编自申请人的摘要） 本项目是制备和表征膨胀卟啉基 受体作为载体的功能，为进入细胞运输 重要的核苷酸类似物，反义 寡脱氧核苷酸和DNA片段。 这种运输代理人可以 大大改善了病毒性疾病的治疗， 临床上可行的新兴领域的反义技术和基因 疗法 迄今为止，已经取得了重大进展。 例如，在一个实施例中， 使用第一组扩展的 基于卟啉的载体证明了这种基本方法将起作用 在实现靶向核苷酸的有效转运中 通过该申请，申请人现在 请提供资金，以便能够延长这项工作。 具体来说，他们 建议为核苷酸制备改进的载体，还请参阅 寡核苷酸运输，并进行细胞研究。 他们将 分以下阶段开展这项拟议工作：1.准备和研究 多位卟啉受体专门设计，以促进进入- 3 '-叠氮基-3'-脱氧胸苷一磷酸的细胞转运， 三磷酸（AZT-MP和TP）和/或9-（2-羟基乙氧基甲基）鸟嘌呤 单磷酸（阿昔洛韦-MP）。 2. 准备和产生胆固醇- 取代的膨胀卟啉，并研究这些作为膜通道， 核苷酸转运 3. 合成含天然膨胀卟啉 特别改性的聚合物，以实现跨膜 反义寡核苷酸和DNA片段的转运。

DESCRIPTION: (Adapted from Applicant's Abstract) The long range goal of this project is to prepare and characterize expanded porphyrin-based receptors that function as carriers for the into-cell transport of pharmacologically important nucleotide analogs, antisense oligodeoxynucleotides, and DNA fragments. Such transport agents could dramatically improve treatment of viral diseases as well as make clinically viable the emerging fields of antisense technology and gene therapy. To date, significant progress has been made. for instance, model U-tube experiments carried out using a first set of expanded porphyrin based carriers demonstrated that this basic approach will work in effecting the efficient transport of targeted nucleotide monophosphates at neutral pH. With this application the applicants now request funds so as to be able to extend this work. Specifically, they propose to prepare improved carriers for nucleotides, look also at oligonucleotide transport, and carry out cellular studies. They will pursue this proposed work in the following stages: 1. Prepare and study polytopic sapphyrin receptors specifically designed to facilitate into- cell transport of 3'-azido-3'-deoxythymidine monophosphate and triphosphate (AZT - MP and TP) and/or 9-(2-hydroxyethoxymethyl) guanine monophosphate (acyclovir-MP). 2. Prepare and generate cholesterol- substituted expanded porphyrins and study these as membrane channels for nucleotide transport. 3. Synthesize expanded porphyrin-bearing natural polymers specifically modified so as to effect the trans-membrane transport of antisense oligonucleotides and DNA fragments.