Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka.
Biol Pharm Bull. 2021;44(1):1-6. doi: 10.1248/bpb.b20-00699.
Protein affinity reagents are widely used for basic research, diagnostics, and disease therapy. Antibodies and their fragments are known as the most common protein affinity reagents. They specifically and strongly bind to target molecules and inhibit their functions. Thus, antibody drugs have increased in the recent two decades for disease therapy, such as cancer. These strong protein-protein interactions are composed of a nexus of multiple weak interactions. Synthetic polymers that bind to target molecules have been developed by the imitation of protein-protein interactions. These polymers show nanomolar affinity for the target and neutralize their functions; thus, they are of significant interest as a cost-effective protein affinity reagent. We have been developing synthetic polymer nanoparticles (NPs) that bind to target peptides and proteins by the inclusion of several functional monomers, such as charged and hydrophobic monomers. In this review, the focus is on the design of synthetic polymer NPs that bind to target molecules for disease therapy. We succeeded in neutralization of toxic peptides and signaling proteins both in vitro and in vivo. Additionally, linear polymers were modified on a lipid nanoparticle surface to improve polymer biodistribution. Our recent findings should provide useful information for the development of abiotic protein affinity reagents.
蛋白质亲和试剂广泛应用于基础研究、诊断和疾病治疗。抗体及其片段是最常见的蛋白质亲和试剂。它们特异性地与靶分子强烈结合，并抑制其功能。因此，在过去二十年中，抗体药物已被广泛用于癌症等疾病的治疗。这些强的蛋白质-蛋白质相互作用由多个弱相互作用的连接组成。通过模仿蛋白质-蛋白质相互作用，已经开发出与靶分子结合的合成聚合物。这些聚合物对靶标具有纳摩尔亲和力，并中和其功能；因此，它们作为一种具有成本效益的蛋白质亲和试剂具有重要的意义。我们一直在开发通过包含几个功能单体（如带电和疏水单体）与靶肽和蛋白质结合的合成聚合物纳米颗粒（NPs）。在这篇综述中，重点介绍了用于疾病治疗的与靶分子结合的合成聚合物 NPs 的设计。我们成功地在体外和体内中和了有毒肽和信号蛋白。此外，线性聚合物在脂质纳米颗粒表面上进行了修饰，以改善聚合物的生物分布。我们最近的发现应该为非生物蛋白质亲和试剂的开发提供有用的信息。
