Molecular Recognition by Bleomycin

博来霉素的分子识别

• 批准号: 8594148
• 负责人: Sidney M. Hecht
• 金额: $ 29.77万
• 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 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8594148
• 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.

描述（由申请人提供）：博来霉素是一类糖肽衍生的抗肿瘤抗生素，最初从轮枝链霉菌中分离出来。一些博莱霉素在临床上用于治疗鳞状细胞癌和恶性淋巴瘤。尽管过去几十年对博莱霉素进行了大量研究，但很少有人涉及博莱霉素的两个显着特性，即其肿瘤寻找特性以及其在生理条件下靶向其 DNA 底物的方式。本项目基于新策略，该策略提供（i）一种用于监测博莱霉素的肿瘤寻找特性的简便方法，以及（ii）一种用于识别博莱霉素高亲和力核酸靶标的方法。该项目的目标包括鉴定博莱霉素中肿瘤靶向所需的结构元件，以及已识别的细胞成分。还提出了鉴定被博来霉素以极高效率结合和切割的 DNA 基序。

项目成果

The carbamoylmannose moiety of bleomycin mediates selective tumor cell targeting.

• DOI: 10.1021/bi500482q
• 发表时间: 2014-05-27
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Bhattacharya C;Yu Z;Rishel MJ;Hecht SM
• 通讯作者: Hecht SM

Characterization of bleomycin-mediated cleavage of a hairpin DNA library.

• DOI: 10.1021/bi400779r
• 发表时间: 2013-08-06
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Segerman ZJ;Roy B;Hecht SM
• 通讯作者: Hecht SM

Hairpin DNA sequences bound strongly by bleomycin exhibit enhanced double-strand cleavage.

• DOI: 10.1021/ja500414a
• 发表时间: 2014-03-19
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Roy, Basab;Hecht, Sidney M.
• 通讯作者: Hecht, Sidney M.

The disaccharide moiety of bleomycin facilitates uptake by cancer cells.

• DOI: 10.1021/ja507255g
• 发表时间: 2014-10-01
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Schroeder, Benjamin R.;Ghare, M. Imran;Bhattacharya, Chandrabali;Paul, Rakesh;Yu, Zhiqiang;Zaleski, Paul A.;Bozeman, Trevor C.;Rishel, Michael J.;Hecht, Sidney M.
• 通讯作者: Hecht, Sidney M.

Selective tumor cell targeting by the disaccharide moiety of bleomycin.

• DOI: 10.1021/ja311090e
• 发表时间: 2013-02-27
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Yu, Zhiqiang;Schmaltz, Ryan M.;Bozeman, Trevor C.;Paul, Rakesh;Rishel, Michael J.;Tsosie, Krystal S.;Hecht, Sidney M.
• 通讯作者: Hecht, Sidney M.