Molecular Recognition by Bleomycin

描述（由申请方提供）：博来霉素是一个糖肽衍生的抗肿瘤抗生素家族，最初分离自轮枝链霉菌。一些博来霉素在临床上用于治疗鳞状细胞癌和恶性淋巴瘤。虽然在过去几十年中已经进行了大量的博来霉素研究，但这些研究中很少有涉及博来霉素的两个显著特性，即其肿瘤寻找特性和其在生理条件下靶向其DNA底物的方式。本项目基于新的策略，其提供（i）用于监测博来霉素的肿瘤寻求特性的简易方法和（ii）用于鉴定博来霉素的高亲和力核酸靶的方法。该项目的目标包括鉴定肿瘤靶向所需的博来霉素结构元件，以及识别的细胞成分。还提出了鉴定被博莱霉素以异常高的效率结合和切割的DNA基序。

DESCRIPTION (provided by applicant): The bleomycins are a family of glycopeptides derived antitumor antibiotics originally isolated from Streptomyces verticillus. Some of the bleomycins are used clinically for the treatment of squamous cell carcinomas and malignant lymphomas. While numerous studies of bleomycin have been carried out in the past few decades, few of these have addressed two remarkable properties of bleomycin, namely its tumor seeking properties and the way in which it targets its DNA substrates under physiological conditions. The present project is based on new strategies which provide (i) a facile method for monitoring the tumor seeking properties of bleomycin and (ii) an approach for identifying high affinity nucleic acid targets for bleomycin. Goals of the project include identification of the structural elements in bleomycin that are required for tumor targeting, as well as the cellular constituents that are recognized. Also proposed is the identification of DNA motifs that are bound and cleaved with exceptionally high efficiency by bleomycin.