MAGNETIC RESONANCE STUDIES OF BIOLOGICAL INTERACTIONS

以不同序列的DNA寡核苷酸为模型 系统，建议调查之间的关系 错配和潜在的承担双螺旋或 发夹结构 我们计划描绘出 发夹，并确定理想的长度和序列 这是相对于双螺旋形成环的要求。 而错配可以产生发夹结构基序。 聚（Pyr）.聚（Pur）序列已在文献中被要求保护 来吸收非ZDNA留下的这种不寻常的结构外来物质- Hoogsteen G=C+成对下绕右手 form. 使用人工合成的poly（pyr）.poly（pur）序列， 将确定这些序列的解结构。 与顺序定向弯曲相关的结构因素将 通过确定选定的解决方案几何形状来描绘 具有已知引起弯曲的序列的低聚物， 不会引起弯曲的相关序列。 将使用500 MHz的2D-NMR光谱进行研究 和相关的光谱工具。 结构将衍生 或者半定量地使用NOE距离， 参与理论和计算机建模。 在少数情况下 结构将定量地从绝对 收集的2D NMR数据中的质子间距离的大小 在自旋扩散效应将被 消除或遏制，并通过使用计算机建模， 精致。 这项建议确定了一些非常刺激的电流 与序列相关的学科中的问题 结构和尝试提供实验设计和 战略来解决它们。 其中一个重要因素， 有助于控制基因组的表达， 结构性的。 因此，要了解的基本基础， 癌症和其他疾病的表达，这是必不可少的知道 双螺旋的详细结构组织，如 由序列驱动。

Using DNA oligonucleotides of different sequences as model systems, it is proposed to investigate the relationships between mismatches and the potentiality to assume double helical or hairpin structures. We plan to delineate the structures of hairpins and to determine the ideal length and sequence requirement for the formation of loops vis-a-vis double helixes. While mismatches can generate hairpin structural motifs. Poly(pyr).poly(pur) sequences have been claimed in the literature to take up such unusual structural exotics as non-ZDNA left- handed form and Hoogsteen G=C+ paired underwound right-handed form. Using synthetic poly(pyr).poly(pur) sequences, the true solution structures of such sequences will be determined. Structural factors associated with sequence directed bending will be delineated by determining the solution geometry of selected oligomers with sequences which are known to cause bending and related sequences which do not cause bending. Studies will be conducted using 2D-NMR spectroscopy at 500 MHz and allied spectroscopic tools. Structures will be derived either semiquantitatively using NOE distances and constructive engagement with theory and computer modelling. In a few cases structures will be derived quantitatively from the absolute magnitude of interproton distances from 2D NMR data collected under conditions in which spin diffusion effects will be eliminated or contained, and by the use of computer modelling for refinement. This proposal identifies some of the very stimulating current problems in the discipline as related to sequence directed structure and attempts to provide experimental design and strategy to solve them. One of the significant factors which contribute to the control of genomic expression must be structural. Hence, to understand the fundamental basis of the expression of cancer and other diseases, it is essential to know the detailed structural organization of the double helix, as driven by the sequence.