Molecular Recognition by Bleomycin

博来霉素的分子识别

• 批准号: 8204865
• 负责人: Sidney M. Hecht
• 金额: $ 30.69万
• 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/8204865
• 关键词: Address; Affinity; B-DNA; Binding; Bleomycin; Cell surface; Characteristics; Cleaved cell; DNA; DNA Binding; Diagnosis; Disaccharides; Drug Delivery Systems; 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. PUBLIC HEALTH RELEVANCE: The bleomycins are used clinically for the treatment of certain tumors that occur in soft tissues. The studies proposed here will facilitate an understanding of the way that this drug targets tumors, and binds to and degrades the nucleic acids in tumor tissue. As such, these studies will enable the preparation of bleomycins with improved properties.

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。 公众健康相关性：博莱霉素在临床上用于治疗软组织中发生的某些肿瘤。这里提出的研究将有助于了解这种药物靶向肿瘤、结合并降解肿瘤组织中的核酸的方式。因此，这些研究将能够制备具有改进特性的博莱霉素。