期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 98, 期 4, 页码 1223-1245出版社
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.21504
关键词
biopharmaceutics; biophysical models; chemical stability; glycosylation; molecular modeling; physical stability; physicochemical properties; proteins; stabilization; thermodynamics
资金
- National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health (NIH) [S06 GM08102]
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 de livery 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. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1223-1245, 2009
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