CYTOTOXICITY OF A RIBONUCLEASE/ANGIOGENIN HYBRID

核糖核酸酶/血管生成素杂合体的细胞毒性

• 批准号: 2429890
• 负责人: L WAYNE SCHULTZ
• 金额: $ 2.86万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-02 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2429890
• 关键词: angiogenesis; cell growth regulation; cytotoxicity; drug design /synthesis /production; hybrid enzyme; pancreatic ribonuclease; protein structure function; site directed mutagenesis; tissue /cell culture

Angiogenin (ANG), a member of the RNase family of proteins, induces blood vessel formation (angiogenesis). ANG has limited, but necessary, ribonuclease activity. Recently, an ANG/ribonuclease A hybrid protein (RNANG), displaying angiogenic activity, was created by replacing an exterior loop in RNase A with the corresponding loop from ANG. The purpose of the research presented in this proposal is to study the molecular basis for cellular recognition and binding, nuclear localization, and the cytotoxicity of ANG and RNANG. Site-directed mutagenesis will be used to create ANG/RNase A hybrid proteins of varying activity and specificity. The ability of the mutants to promote/inhibit angiogenesis in vivo will be assessed. Effects on cellular growth rate and cytotoxicity will be screened against a panel of endothelial and tumor cells selected by their ability to internalize RNANG. A fundamental understanding of angiogenic activity would ideally lead to developing a therapeutic control of blood vessel formation in tumor growth and metastasis.

血管生成素（ANG）是核糖核酸酶家族的一员， 血管形成（血管生成）。 ANG拥有有限但必要的， 核糖核酸酶活性 最近，ANG/核糖核酸酶A杂合蛋白， （RNANG），显示血管生成活性，是通过替换 RNA酶A中的外部环与来自ANG的相应环。 目的 这项建议中提出的一项研究是研究分子基础 用于细胞识别和结合，核定位，以及 ANG和RNAG的细胞毒性。 将使用定点诱变来 产生不同活性和特异性的ANG/RNase A杂合蛋白。 突变体在体内促进/抑制血管生成的能力将被评估。 评估。 将研究对细胞生长速率和细胞毒性的影响。 筛选了一组内皮细胞和肿瘤细胞， 使RNANG内在化的能力。 对血管生成的基本理解 理想情况下，活性将导致开发血液的治疗控制 血管形成在肿瘤生长和转移中的作用