Growth hormone receptor agonists and antagonists: From protein expression and purification to long-acting formulations

被引：4
|
作者：
Wang, Yue [1 ,2 ]
Kim, Minah [1 ]
Buckley, Chantal [1 ]
Maynard, Heather D. D. [3 ,4 ]
Langley, Ries J. J. [2 ,5 ]
Perry, Jo K. K. [1 ,2 ]
机构：
[1] Univ Auckland, Liggins Inst, 85 Pk Rd,Private Bag 92019, Auckland 1142, New Zealand
[2] Maurice Wilkins Ctr Mol Biodiscovery, Auckland, New Zealand
[3] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA USA
[4] Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA USA
[5] Univ Auckland, Dept Mol Med & Pathol, Auckland, New Zealand
来源：
PROTEIN SCIENCE | 2023年 / 32卷 / 09期
关键词：
growth hormone; antagonist; recombinant protein production; long-acting; PEGylation; fusion protein; biotherapeutic; SITE-SPECIFIC PEGYLATION; HIGH-LEVEL EXPRESSION; PREPARATION NUTROPIN DEPOT; SINGLE-STEP PURIFICATION; P-L PROMOTER; ESCHERICHIA-COLI; PICHIA-PASTORIS; HETEROLOGOUS PROTEIN; INCLUSION-BODIES; HUMAN GH;
D O I：
10.1002/pro.4727
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Recombinant human growth hormone (rhGH) and GH receptor antagonists (GHAs) are used clinically to treat a range of disorders associated with GH deficiency or hypersecretion, respectively. However, these biotherapeutics can be difficult and expensive to manufacture with multiple challenges from recombinant protein generation through to the development of long-acting formulations required to improve the circulating half-life of the drug. In this review, we summarize methodologies and approaches used for making and purifying recombinant GH and GHA proteins, and strategies to improve pharmacokinetic and pharmacodynamic properties, including PEGylation and fusion proteins. Therapeutics that are in clinical use or are currently under development are also discussed.
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收藏
页数：33
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