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治疗性蛋白质在整个运输过程中的修饰的生物学见解及其生物制药应用。

Biological Insights into Therapeutic Protein Modifications throughout Trafficking and Their Biopharmaceutical Applications.

作者信息

Zhong Xiaotian, Wright Jill F

机构信息

Pfizer BioTherapeutics Research & Development, 87 Cambridge Park Drive, Cambridge, MA 02140, USA.

出版信息

Int J Cell Biol. 2013;2013:273086. doi: 10.1155/2013/273086. Epub 2013 Apr 18.

DOI:10.1155/2013/273086
PMID:23690780
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3652174/
Abstract

Over the lifespan of therapeutic proteins, from the point of biosynthesis to the complete clearance from tested subjects, they undergo various biological modifications. Therapeutic influences and molecular mechanisms of these modifications have been well appreciated for some while remained less understood for many. This paper has classified these modifications into multiple categories, according to their processing locations and enzymatic involvement during the trafficking events. It also focuses on the underlying mechanisms and structural-functional relationship between modifications and therapeutic properties. In addition, recent advances in protein engineering, cell line engineering, and process engineering, by exploring these complex cellular processes, are discussed and summarized, for improving functional characteristics and attributes of protein-based biopharmaceutical products.

摘要

在治疗性蛋白质的整个生命周期中,从生物合成到从受试对象中完全清除,它们会经历各种生物学修饰。这些修饰的治疗作用和分子机制在一段时间内已得到充分认识,但仍有许多尚不清楚。本文根据这些修饰在运输过程中的加工位置和酶的参与情况,将其分为多个类别。它还关注修饰与治疗特性之间的潜在机制以及结构 - 功能关系。此外,还讨论并总结了通过探索这些复杂细胞过程,在蛋白质工程、细胞系工程和工艺工程方面的最新进展,以改善基于蛋白质的生物制药产品的功能特性和属性。

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