Structural and Biochemical Analysis of Telomerase Function

端粒酶功能的结构和生化分析

基本信息

批准号：
8286908
负责人：
Emmanuel Skordalakes
金额：
$ 32.7万
依托单位：
WISTAR INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8286908
关键词：
3-Dimensional Address Affinity Aging Amino Acids Antineoplastic Agents Binding Biochemical Biochemistry Biological Assay Biological Process Cardiovascular Diseases Catalysis Cell Aging Cell Proliferation Cells Chromosomes Complementary DNA Complex DNA DNA Binding DNA Sequence DNA biosynthesis Data Disease Drug Delivery Systems Elongation by Telomerase Enzymes Evolution Eye Functional disorder Genome Goals Holoenzymes Homeostasis Human In Vitro Ions Laboratories Length Literature Malignant Neoplasms Maps Metals Methods Modeling Molecular Mutagenesis Nucleic Acids Nucleotides Polymerase Positioning Attribute Process Proteins Protocols documentation RNA RNA Recognition Motif RNA-Directed DNA Polymerase Recombinants Research Resolution Ribonucleoproteins Role Scientist Structure System Techniques Telomerase Telomerase Inhibitor Telomerase RNA Component Testing Tetrahymena thermophila Therapeutic Time Tribolium Work age related base cancer cell cancer therapy cell age combat deoxyguanosine triphosphate design drug discovery electron density human disease insight mutant novel overexpression programs public health relevance reconstitution research study small molecule structural biology telomerase reverse transcriptase telomere tool tumor

项目摘要

DESCRIPTION (provided by applicant): Inappropriate activation of a single enzyme, telomerase, is associated with the uncontrolled proliferation of cells seen in as many as 90 percent of all human cancers. Since the mid-1990s, when telomerase was first identified in human tumors, scientists have eyed the enzyme as an ideal target for developing broadly effective anti-cancer drugs. The important role of telomerase in cancer makes this enzyme an important drug target. I propose a structural biology approach to examine the function of telomerase and its role in human disease. Structural data can prove invaluable in explaining, as well as designing, biochemical and biophysical experiments. It can also be a very powerful tool for drug discovery. The long-term goal of my research plan is to use structural biology, in conjunction with biochemistry to understand how telomerase replicates telomere ends, and to apply this information to the pursuit of anti-cancer therapies. PUBLIC HEALTH RELEVANCE: Telomerase has been implicated in cancer, cardiovascular disease and aging. For this reason, our goal is to elucidate the biological function of this enzyme and use this information to combat cancer and age-related diseases.

描述（由申请人提供）：单个酶，端粒酶的不适当激活与多达90％的所有人类癌症中的细胞的不受控制相关。自1990年代中期以来，当端粒酶在人类肿瘤中首次鉴定时，科学家将酶视为开发广泛有效的抗癌药物的理想靶标。端粒酶在癌症中的重要作用使该酶成为重要的药物靶标。我提出了一种结构生物学方法，以检查端粒酶的功能及其在人类疾病中的作用。结构数据在解释以及设计，生化和生物物理实验方面可能是无价的。它也可能是一种非常有力的药物发现工具。我的研究计划的长期目标是将结构生物学与生物化学结合使用，以了解端粒酶如何复制端粒结束，并将这些信息应用于追求抗癌疗法。公共卫生相关性：端粒酶与癌症，心血管疾病和衰老有关。因此，我们的目标是阐明该酶的生物学功能，并使用此信息来打击癌症和与年龄有关的疾病。