RESPONSIVE POLYMER ENGINEERED PROTEIN CONJUGATES

这一竞争性更新提议的具体目标是开发作为分子开关的刺激反应生物偶联物和络合物，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”)。生物活性开关是一种响应性的聚合物工程蛋白(RP-EP)结合物，可以被刺激来开启和关闭蛋白质的活性，或者触发结合配体的释放。作为开关的应用包括亲和分离、诊断、药物靶向和酶工艺，如聚合酶链式反应、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：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的传递。这种行动在医学、生物技术和工业中有许多不同的用途。膜开关是一种pH响应性的聚合物生物偶联物或与药物载体的复合体，它破坏内膜以增强DNA或蛋白质药物在细胞内的输送。这种作用应该会增加基因、反义寡核苷酸和癌症治疗的效率。

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.