DESIGN AND SYNTHESIS OF OLIGONUCLEOTIDE ANALOGS

描述：（改编自申请人摘要）。的主要专题 这项研究计划是开发修饰的寡核苷酸， 其在正常条件下催化序列特异性核酸切割 细胞条件。 此外，一项研究，以确定潜在的 用于靶向针对卡氏肺孢子虫的反义寡核苷酸 将被追究。 具体目标是：（1）确定机制， 建立铁介导的序列特异性切割的范围， 核酸通过菲咯啉拴系的寡核苷酸;（2）构建 第二代金属结合修饰的寡核苷酸， 高特异性氧化还原介导的链间切割;（3）开发 专门设计的组合修饰寡核苷酸文库 结合金属离子（Mg 2+、Zn 2+或Ca 2+）以寻找新的序列- 特异性核酸酶;（4）探索dsDNA的链侵入策略 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;和 (6)研究卡氏肺孢子虫作为反义核酸的潜在靶点 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.