NUCLEOSIDE PHOSPHATE ANALOGUES WITH BORONATED PHOSPHATES

含硼磷酸盐的核苷磷酸类似物

• 批准号: 3489416
• 负责人: BERNARD F SPIELVOGEL
• 金额: $ 4.99万
• 依托单位: BORON BIOLOGICALS, INC.
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3489416
• 关键词: antineoplastics; antiviral agents; boron; cell membrane; chemical stability; cytotoxicity; drug design /synthesis /production; enzyme induction /repression; enzyme mechanism; membrane permeability; neutron radiation; nuclease; nucleic acid chemical synthesis; nucleotide analog; nucleotide metabolism; phosphates; phosphorylation; radionuclide therapy; stereochemistry; synthetic nucleotide

DESCRIPTION: (Adapted from the applicant's abstract) Use of nucleoside phosphates as antitumor and antiviral agents has been limited by their inability to penetrate cell membranes as well as their high susceptibility to enzymes such as phosphatases, nucleotidases, etc. Modification of the phosphate group (by replacing one of the nonbridging oxygens with a borane group) may provide both the membrane permeability to these compounds and the stability (towards phosphate-removing enzymes). The long term objective of this project is to synthesize nucleoside mono-, di-and triphosphates in which one of the oxygens of alpha, beta or gamma phosphorus has been replaced with an isoelectric borane group. These compounds may be prepared by phosphorylation of nucleosides, nucleoside monophosphates and nucleoside diphosphates using a boronated phosphorylating agent. In their studies with related oligonucleotide boranophosphates, the P-BH3 moiety has been found to be remarkably stable and the oligonucleotide boranophosphates have high nuclease resistance. The nucleoside boranophosphates may be useful in a number of ways including: l) as tools for studying mechanism of action of enzymes, 2) as antiviral and antitumor agents, and 3) as carriers of boron neutron capture therapy.

描述：（改编自申请人的摘要）使用核苷 磷酸盐作为抗肿瘤和抗病毒剂已受其限制 无法穿透细胞膜及其高易感性 用于诸如磷酸酶，核苷酸酶等酶。修饰 磷酸盐组（通过用硼烷代替非桥梁的氧气之一 组）可以同时向这些化合物提供膜渗透性，并且 稳定性（朝着磷酸盐驱动的酶）。 该项目的长期目的是合成核苷单一目标 Di-and三磷酸盐，其中一种α，β或伽玛的氧 磷已被等电硼烷组取代。 这些 化合物可以通过核苷，核苷的磷酸化制备 单磷酸和核苷双磷酸盐使用卫生 磷酸化剂。 在与相关寡核苷酸的研究中 硼烷磷酸盐，已经发现P-BH3部分非常稳定 并且寡核苷酸硼苯磷酸盐具有较高的核酸酶耐药性。 核苷的硼烷磷酸盐可能以多种方式有用 包括：l）作为研究酶作用机理的工具，2） 抗病毒和抗肿瘤剂，3）作为硼中子捕获的载体 治疗。