RESPONSIVE POLYMER ENGINEERED PROTEIN CONJUGATES

这一竞争性更新提案的具体目标是开发刺激反应性生物偶联物和复合物作为控制(a)生物识别过程（“生物活性开关”）和(b)细胞内生物分子运输（“膜开关”）的分子开关。生物活性开关是反应性聚合物工程蛋白（RP-EP）偶联物，可以通过刺激来开启和关闭蛋白质活性，或触发结合配体的释放。作为开关的应用包括亲和分离，诊断，药物靶向和酶过程，如PCR，工业酶过程和洗涤剂和织物整理过程。生物活性开关作为触发释放系统的作用包括：生物素化剂、亲和生物分子、药物、化学剂、酶底物、产物或抑制剂和信号的传递。这种行为在医学、生物技术和工业中有许多不同的用途。膜开关是ph响应聚合物生物偶联物或药物载体复合物，破坏内体膜以增强DNA或蛋白质药物的细胞内递送。这一作用将增加基因、反义寡核苷酸和癌症治疗的疗效。

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.