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: 2712771
• 负责人: L WAYNE SCHULTZ
• 金额: $ 3.05万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-02 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2712771
• 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（Angiogenin， ANG）是RNase蛋白家族的一员，可诱导血液生成

项目成果

Variants of ribonuclease inhibitor that resist oxidation.

抗氧化的核糖核酸酶抑制剂的变体。

• DOI: 10.1110/ps.8.2.430
• 发表时间: 1999
• 期刊: Protein science : a publication of the Protein Society
• 作者: Kim,BM;Schultz,LW;Raines,RT
• 通讯作者: Raines,RT