Effects of glycosylation on the stability of protein pharmaceuticals.
Effects of glycosylation on the stability of protein pharmaceuticals.
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DOI：
10.1002/jps.21504
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发表时间：
2009-04
影响因子：
3.8
通讯作者：
Griebenow, Kai
中科院分区：
文献类型：
--
作者：
Sola, Ricardo J.;Griebenow, Kai
关键词：
近几十年来，基于蛋白质的治疗剂由于其治疗疾病的突出潜力而大大扩展了分子药理学领域。不幸的是，蛋白质药物在其生产、纯化、储存和递送过程中显示出一系列内在的物理和化学不稳定性问题，这些问题可能不利地影响其最终治疗功效。这促使人们积极寻找通用策略来设计蛋白质在制药过程中的长期稳定性。由于聚糖在增加糖蛋白的整体稳定性方面具有众所周知的作用，通过糖工程合理操纵糖基化参数可能成为改善蛋白质药物的体外和体内稳定性的有前途的方法。因此，本综述的目的是通过增加对糖基化改善蛋白质药物分子稳定性的机制的一般理解来进一步推进蛋白质糖工程领域。这是通过提出一个调查的蛋白质药物显示的不同的不稳定性，通过解决这些不稳定性，可以改善糖基化，并通过讨论可能的机制，聚糖诱导这些稳定的效果。
In recent decades, protein-based therapeutics have substantially expanded the field of molecular pharmacology due to their outstanding potential for the treatment of disease. Unfortunately, protein pharmaceuticals display a series of intrinsic physical and chemical instability problems during their production, purification, storage, and delivery that can adversely impact their final therapeutic efficacies. This has prompted an intense search for generalized strategies to engineer the long-term stability of proteins during their pharmaceutical employment. Due to the well known effect that glycans have in increasing the overall stability of glycoproteins, rational manipulation of the glycosylation parameters through glycoengineering could become a promising approach to improve both the in vitro and in vivo stability of protein pharmaceuticals. The intent of this review is therefore to further the field of protein glycoengineering by increasing the general understanding of the mechanisms by which glycosylation improves the molecular stability of protein pharmaceuticals. This is achieved by presenting a survey of the different instabilities displayed by protein pharmaceuticals, by addressing which of these instabilities can be improved by glycosylation, and by discussing the possible mechanisms by which glycans induce these stabilization effects.
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单点突变对蛋白质稳定性的三态预测发生了变化。
影响因子：
3
作者：
Capriotti, Emidio;Fariselli, Piero;Rossi, Ivan;Casadio, Rita
通讯作者：
Casadio, Rita
影响因子：
2.9
作者：
Bagger, HL;Fuglsang, CC;Westh, P
通讯作者：
Westh, P
影响因子：
10.8
作者：
Castellanos, IJ;Cruz, G;Griebenow, K
通讯作者：
Griebenow, K
影响因子：
5.5
作者：
Carter, CRD;Whitmore, KM;Thorpe, R
通讯作者：
Thorpe, R
影响因子：
5.8
作者：
Capriotti, E;Fariselli, P;Casadio, R
通讯作者：
Casadio, R