DRUG INDUCED DNA DEGRADATION: BLEOMYCIN, ANTI TUMOR, ANTIBIOTIC

我们正在努力了解 抗肿瘤抗生素博来霉素（BLM）的双链切割 并确定DNA损伤的结构， 序列上下文，由BLM和其他小的 DNA分子。 我们开发了一种新的合成方法， 具有3 '磷酸乙醇酸酯的单链拴系寡聚DNA 任何序列背景下的病变。 我们合成了一个病灶， 获得的核磁共振谱，使我们能够分配几乎所有的 质子 目前，我们正在进行分子 使用迄今为止获得的420个NOE进行建模。

We are trying to understand the chemistry and biology of double-stranded cleavage by the antitumor antibiotic bleomycin (BLM) and to determine the structures of the DNA lesions, in differew sequence contexts, generated by the interaction of BLM and other small molecules with DNA. We have developed a new method to synthesize a single strand of tethered oligomeric DNA with a 3'phosphoglycolate lesion in any sequence context. We have synthesized a lesion and acquired NMR spectra that have allowed us to assign almost all of the protons. Currently, we are in the process of performing molecular modeling using the 420 NOEs obtained thus far.