Enzyme and Microbial Biochemistry Laboratory, Department of Chemistry, Indian Institute of Technology Delhi, New Delhi, India.
Department of Chemical Engineering, Indian Institute of Technology Delhi, New Delhi, India.
Adv Exp Med Biol. 2019;1148:131-150. doi: 10.1007/978-981-13-7709-9_7.
Enzymes are biocatalysts that have found profound applications in the current biotherapeutic industry and play a crucial role in diagnosis, prevention, and biochemical analysis of major diseases. However, stability, protein degradation and immunogenicity in the body present unique challenges that are faced upon sustained use of such enzymes. The present chapter is an attempt to dissect the state-of-the-art in relation to the challenges of development of therapeutic enzymes and the recent advances to address them. At the very outset, diseases where enzymes have found effective applications and the various causes of enzyme instability have been discussed. In recent times, polymer or nano- conjugated resistant delivery methods, as well as mutagenesis have led to manifold increase in enzyme stability against thermal denaturation, acidic gut environment, proteolysis and immunogenicity. Further, methods of analytical characterization of proteins have been highlighted and explored to shape future research directions.
酶是生物催化剂，在当前的生物治疗行业中有着广泛的应用，在重大疾病的诊断、预防和生化分析中起着关键作用。然而，在持续使用这些酶时，其在体内的稳定性、蛋白质降解和免疫原性带来了独特的挑战。本章试图剖析与治疗性酶的开发挑战相关的最新进展。首先，讨论了酶在哪些疾病中得到了有效应用以及导致酶不稳定的各种原因。最近，聚合物或纳米共轭抗性传递方法以及诱变导致酶的热变性、酸性肠道环境、蛋白水解和免疫原性稳定性大大提高。此外，还强调和探讨了蛋白质分析特性的方法，以塑造未来的研究方向。
