DESIGN AND SYNTHESIS OF OLIGONUCLEOTIDE ANALOGS

描述：(改编自申请人摘要)。的主旋律 本研究的建议是开发修饰的寡核苷酸 在正常情况下催化序列特异性核酸裂解 细胞条件。此外，一项研究确定了潜在的 靶向卡氏肺孢子虫反义寡核苷酸的研究 将会被追查。具体目标是：(1)确定机制和 确定铁介导的序列特异性切割的范围 邻菲咯啉连接的寡核苷酸构建核酸； 第二代金属结合修饰寡核苷酸 高特异性氧化还原介导的链间切割；(3)发展 专门设计的组合修饰寡核苷酸文库 结合金属离子(镁、锌、钙)寻找新的序列- 特异性核酸酶；(4)探索dsDNA的链侵袭策略 靶向和切割；(5)确定寡核苷酸的潜力 用于金属介导的DNA链间交联的附加配体；以及 (6)研究卡氏肺孢子虫作为反义靶标的可能性 寡核苷酸。

DESCRIPTION: (Adapted from Applicant's Abstract). The principal theme of this research proposal is the development of modified oligonucleotides that catalyze sequence-specific nucleic acid cleavage under normal cellular conditions. In addition, a study to determine the potential for targeting antisense oligonucleotides against Pneumocystis carinii will be pursued. Specific aims are: (1) Determine mechanism and establish scope of the iron mediated sequence-specific cleavage of nucleic acids by phenanthroline tethered oligonucleotides; (2) Construct second generation metal binding modified oligonucleotides designed for high specificity redox-mediated interstrand cleavage; (3) Develop combinatorial modified oligonucleotide libraries specifically designed to bind metal ions (Mg2+, Zn2+, or Ca2+) to search for new sequence- specific nucleases; (4) Explore strand-invasion strategies for dsDNA targeting and cleavage; (5) Determine the potential of oligonucleotide appended ligands for metal-mediated DNA interstrand cross- linking; and (6) Investigate P. carinii as a potential target for antisense oligonucleotides.