PEPTIDE DNA HYBRIDS

我们对确定高分辨率结构很感兴趣 多肽-DNA杂交物和利用这些结构寻找新的 与DNA或RNA靶标结合的治疗剂。特别是， 与单链紧密结合的多肽序列 寡核苷酸，从而保护它们免受核酸酶的降解 正在被追捕。根据体外选择的结果 实验中，选择了两个肽-DNA序列。二维图 第一个序列(KWKGSGCTTTGAC)的光谱(NOESY，TOCSY)是 记录并尽管优化了盐浓度、pH和 温度，光谱没有提供足够的限制 解决了三维结构的高度柔性化 分子内复合体。第二个序列(WTG-CGCAC)已经 选自部分自互补序列，其中 氨基酸残基与单链的相互作用 区域被双面的模板效果所青睐。NOESY 所选杂化分子在40、80、160、320和500ms的光谱 记录混合时间以及TOCSY和ROESY 做实验。这些光谱被发现包含了丰富的 分辨率很好的交叉峰，使我们能够指定许多质子 在混合动力车里。初步的分子动力学工作就是这样进行的 远用“模拟退火法”套路的X-plor导致了非常 第一套不精致的结构。基于这些，我们有信心 我们将能够解决这个综合体的结构。

We are interested in determining high resolution structures of peptide-DNA hybrids and using these structures to search for new therapeutic agents that bind to DNA or RNA targets. In particular, peptide sequences that bind tightly to single-stranded oligonucleotides, and thus protect them against nuclease degradation are being sought. Based on the results of the in vitro selection experiments, two peptide-DNA sequences were selected. Two-dimensional spectra (NOESY, TOCSY) of the first sequence (KWKGSGCTTTGAC) were recorded and despite optimization of salt concentration, pH, and temperature, the spectra did not provide sufficient constraints to solve the three-dimensional structure of the highly flexible intramolecular complex. The second sequence (WTG-CGCAC) had been selected from partially self-complementary sequences, where interactions between amino acid residues and the single-stranded region are favored by the template effect of the duplex. NOESY spectra of the chosen hybrid molecule at 40, 80, 160, 320, and 500 ms mixing time were recorded, together with a TOCSY and a ROESY experiment. These spectra were found to contain a rich collection of well resolved cross peaks, allowing us to assign many of the protons in the hybrid. The preliminary molecular dynamics work performed so far with the "simulated annealing" routine of X-PLOR led to a very first set of unrefined structures. Based on these, we are confident that we will be able to solve the structure of this complex.