DESIGN OF SEQUENCE SPECIFIC METAL POLYAMIDE CONJUGATES

描述了结合DNA小沟内预定序列的DNA靶向过渡金属络合物和发夹聚酰胺的第一序列特异性缀合物的设计。吡咯-咪唑-羟基吡咯聚酰胺发夹被专门设计为识别单个核苷酸序列，将被用作识别系统，将过渡金属络合物递送到所需的多核苷酸位点。随后在DNA和过渡金属络合物之间形成共价键将使缀合物固定在所需的核苷酸位点。预期氢键和共价键的这种组合抑制聚合酶II和III的进行性运动，从而干扰基因表达的机制。将制备三种不同的过渡金属络合物，Pt（II）、Pt（IV）和二茂金属，并通过NMR和各种核酸技术研究它们的结合亲和力和序列特异性。

The design of the first sequence-specific conjugates of DNA-targeting transition metal complexes and hairpin polyamides that bind to a predetermined sequence within the DNA minor groove is described. Pyrrole-imidazole-hydroxypyrrole polyamide hairpins that are specifically designed to recognize a single nucleotide sequence will be used as a recognition system, delivering the transition metal complexes to the desired polynucleotide site. Subsequent formation of a covalent bond between DNA and the transition metal complex will secure the conjugate in the desired nucleotide site. Such a combination of hydrogen-bonding and covalent bonds is expected to inhibit the progressive movement of polymerase II and III thereby interfering with the mechanism of gene expression. Three different transition metal complexes, Pt(II), Pt(IV) and molybdenocene will be prepared and their binding affinity and sequence specificity will be investigated by NMR and various nucleic acid techniques.