RESPONSIVE POLYMER ENGINEERED PROTEIN CONJUGATES

响应性聚合物工程蛋白缀合物

• 批准号: 2849107
• 负责人: ALLAN S HOFFM
• 金额: $ 26.04万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-02-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2849107
• 关键词: acidity /alkalinity; binding proteins; binding sites; biotin; chemical association; chemical binding; chemical conjugate; chemical synthesis; enzyme substrate; flow cytometry; fluorescence microscopy; molecular weight; monoclonal antibody; nucleic acid sequence; polymerase chain reaction; polymers; protein engineering; protein structure; site directed mutagenesis; subtilisins; temperature

The specific aims of this competitive renewal proposal are to develop stimuli-responsive bioconjugates and complexes as molecular switches for controlling (a) biorecognition processes ("bioactivity switches") and (b) intracellular trafficking of biomolecules ("membrane switches"). Bioactivity switches are responsive polymer-engineered protein (RP-EP) conjugates that can be stimulated to turn protein activity on and off , or trigger release of bound ligand. Applications as on-off switches include affinity separations, diagnostics, drug targeting, and enzyme processes, such as PCR, industrial enzyme processes and detergent and fabric finishing processes. Actions of bioactivity switches as triggered release systems include the delivery of: biotinylated agents, affinity biomolecules, drugs, chemical agents, enzyme substrates, products or inhibitors, and signals. Such actions have many diverse uses in medicine, biotechnology and industry. Membrane switches are pH-responsive polymer bioconjugates or complexes with drug carriers that disrupt endosomal membranes to enhance intracellular delivery of DNA or protein drugs. This action should increase the efficacies of gene, antisense oligonucleotide, and cancer therapies.

该竞争性更新提案的具体目标是开发刺激响应性生物缀合物和复合物作为用于控制（a）生物识别过程（“生物活性开关”）和（B）生物分子的细胞内运输（“膜开关”）的分子开关。 生物活性开关是响应性聚合物-工程化蛋白质（RP-EP）缀合物，其可以被刺激以打开和关闭蛋白质活性，或触发结合配体的释放。 作为开关开关的应用包括亲和分离、诊断、药物靶向和酶工艺，例如PCR、工业酶工艺以及洗涤剂和织物整理工艺。 作为触发释放系统的生物活性开关的作用包括递送：生物素化试剂、亲和生物分子、药物、化学试剂、酶底物、产物或抑制剂以及信号。这种行动在医学、生物技术和工业中有许多不同的用途。 膜开关是pH响应性聚合物生物缀合物或与药物载体的复合物，其破坏内体膜以增强DNA或蛋白质药物的细胞内递送。 这一行动将增加基因、反义寡核苷酸和癌症治疗的功效。