Molecular Recognition by Bleomycin

博来霉素的分子识别

• 批准号: 8403820
• 负责人: Sidney M. Hecht
• 金额: $ 28.85万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-18 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8403820
• 关键词: Address; Affinity; B-DNA; Binding; Bleomycin; Cell surface; Characteristics; Cleaved cell; DNA; DNA Binding; Diagnosis; Disaccharides; Drug Targeting; Elements; Family; Glycopeptides; Goals; Investigation; Lymphoma; Mediating; Methods; Molecular; Monitor; Nucleic Acids; Physiological; Preparation; Property; RNA; Research; Squamous cell carcinoma; Streptomyces; Tumor Tissue; analog; antineoplastic antibiotics; antitumor agent; base; cancer cell; improved; indium-bleomycin; molecular recognition; public health relevance; soft tissue; tumor

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.

说明(申请人提供)：博莱菌素是一类糖肽类抗肿瘤抗生素，最初从轮纹链霉菌中分离出来。一些博莱霉素被用于临床治疗鳞状细胞癌和恶性淋巴瘤。尽管在过去的几十年里，人们对博莱霉素进行了大量的研究，但很少有研究涉及博莱霉素的两个显著特性，即它的肿瘤寻找特性和它在生理条件下靶向DNA底物的方式。本项目基于新的策略，这些策略提供了(I)监测博莱霉素的找瘤特性的简便方法和(Ii)识别博莱霉素的高亲和力核酸靶标的方法。该项目的目标包括鉴定肿瘤靶向所需的博莱霉素中的结构成分，以及被识别的细胞成分。还提出了用博莱霉素非常高效地结合和切割DNA基序的鉴定方法。