Walsh Gary, Jefferis Roy
Industrial Biochemistry Program, University of Limerick, Castletroy, Limerick City, Ireland.
Nat Biotechnol. 2006 Oct;24(10):1241-52. doi: 10.1038/nbt1252.
The majority of protein-based biopharmaceuticals approved or in clinical trials bear some form of post-translational modification (PTM), which can profoundly affect protein properties relevant to their therapeutic application. Whereas glycosylation represents the most common modification, additional PTMs, including carboxylation, hydroxylation, sulfation and amidation, are characteristic of some products. The relationship between structure and function is understood for many PTMs but remains incomplete for others, particularly in the case of complex PTMs, such as glycosylation. A better understanding of such structural-functional relationships will facilitate the development of second-generation products displaying a PTM profile engineered to optimize therapeutic usefulness.
大多数已获批或正在进行临床试验的基于蛋白质的生物制药都带有某种形式的翻译后修饰（PTM），这可能会深刻影响与其治疗应用相关的蛋白质特性。虽然糖基化是最常见的修饰，但其他翻译后修饰，包括羧化、羟基化、硫酸化和酰胺化，是某些产品的特征。许多翻译后修饰的结构与功能之间的关系已为人所知，但其他一些翻译后修饰的关系仍不完整，特别是在复杂的翻译后修饰（如糖基化）的情况下。更好地理解这种结构-功能关系将有助于开发第二代产品，这些产品具有经过设计以优化治疗效用的翻译后修饰谱。
