X-RAY STUDIES ON NUCLEIC ACID CONSTITUENTS

核酸成分的 X 射线研究

基本信息

批准号：
3269099
负责人：
MUTTAIYA SUNDARALINGAM
金额：
$ 4万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-09-01 至 1991-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3269099
关键词：
X ray crystallography antineoplastic antibiotics antineoplastics chemical models conformation gene expression metal complex nuclear magnetic resonance spectroscopy nucleic acid chemical synthesis nucleic acid sequence nucleic acid structure nucleobase nucleoside monophosphate oligonucleotides polynucleotides stereochemistry

项目摘要

The objectives of this proposal are to determine the crystal and molecular structures of selected nucleic acid constituents with the view of understanding their biological properties, interactions and functions. Structural studies are underway on: (a) metal-nucleotide and metal-polyphosphate complexes, (b) modified nucleosides and nucleotides including alkylated nucleotides, (c) deoxyoligonucleotides and DNA fragments and (d) drug- and dye-nucleotide complexes. Studies are underway on metal complexes containing mixed ammine and aquo ligands, sulphur substitution in the phosphate and also to metal ions such as rhodium in addition to Cr3+, Zn2+, Mn2+, Co2+, Ca2+ and Mg2+. The metal-nucleotide and metal-polyphosphate studies are being done in collaboration with Dr. Dunaway-Mariano (Univ. of Maryland), Dr. Richard Cornelius (Univ. of Wichita), Dr. W. Wallace Cleland (Univ. of Wisconsin), and Dr. Renzo Cini (Univ. of Florence). X-ray structures and NMR investigations of modified nucleosides and base O-alkylated nucleosides are being carried out in collaboration with Dr. Frank Hruska (Univ. of Manitoba) and phosphate O-alkylated nucleotides in collaboration with Dr. Norman Kondo (Univ. District of Columbia, Washington, DC). Studies are underway on the following deoxyoligonucleotides (ii) CGTACGTACG, (iii) CGTATATACG and (iii) CGCGCCCCGCG. (i) and (ii) have already been crystallized. We are also setting up facilities for DNA oligomer synthesis. The above structural studies will provide information on variability in nucleic acid structures, and principles controlling coordination of nucleotides which aid our understanding of the use of metal-substrates as probes in enzyme specificity and mechanism. The work on oligonucleotides will provide useful information on sequence-dependent conformational variations in DNA structure which is important in understanding gene expression and regulation.

该提案的目标是确定晶体和分子选定的核酸成分的结构了解它们的生物学特性，相互作用和功能。结构研究正在进行：（a）金属核苷酸和金属 - 聚磷酸酯络合物，（b）修饰的核苷和核苷酸包括烷基化核苷酸，（C）脱氧乙烯核苷酸和DNA 碎片以及（d）药物和染料核苷酸复合物。研究正在进行中在含有混合胺和含水配体的金属络合物上，硫在磷酸盐中取代，也取代金属离子，例如与CR3+，Zn2+，MN2+，CO2+，Ca2+和Mg2+相加。金属核苷酸与Dr. 杜纳威·马里亚诺（Dunaway-Mariano）（马里兰州大学）威奇托），W。WallaceCleland博士（威斯康星州大学）和Renzo Cini博士（佛罗伦萨大学）。修改的X射线结构和NMR研究核苷和碱基O-烷基化核苷在与弗兰克·赫鲁斯卡（Frank Hruska）博士（曼尼托巴大学）和磷酸盐合作 O-烷基化的核苷酸与Norman Kondo博士合作（Univ。华盛顿特区哥伦比亚特区）。研究正在进行在脱氧乙烯核苷酸（II）CGTACGTACG，（III）CGTATATACG和（III）之后 CGCGCCCCGCG。（i）和（ii）已经结晶。我们也是设置DNA低聚物合成的设施。上述结构研究将提供有关核酸结构变异性的信息，以及控制核苷酸协调的原理，这有助于我们了解金属材料作为酶中的探针的使用特异性和机制。关于寡核苷酸的工作将提供 DNA中依赖序列构象变化的有用信息结构对于理解基因表达和规定。