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）核苷的使用