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Chemical Research in Chinese Universities

, Volume 34, Issue 3, pp 428–433 | Cite as

Site-specific PEGylation of Human Growth Hormone by Mutated Sortase A

  • Hui Shi
  • Qingyang Shi
  • James T. Oswald
  • Ying Gao
  • Leijiao Li
  • Yunhui Li
Article
  • 22 Downloads

Abstract

Human growth hormone(hGH), a classic therapeutic protein, which promotes growth and wound healing, is released from the pituitary gland. As a protein drug, its short half-life is its main barrier to therapeutic efficacy. Various strategies have been designed to prolong its serum half-life, the most common of which is the conjugation with polyethylene glycol(PEG), as this has been shown to significantly extend protein’s serum half-life. However, PEGylation often results in random conjugation, which can lead to impaired protein function and hinder purification, characterization and evaluation of the PEGylated protein. Therefore, site specific PEGylation is a promising direction for PEG-protein conjugation. Here we took advantages of the mutated sortase A(7M) enzyme, which can enzymatically ligate the universal α-amino acids to a C-terminal tagged protein. This then allows specific modification of the C-terminal of hGH with PEG. This site-specific bound PEG-hGH has similar efficacy, receptor binding and cell proliferation as wild-type hGH; however, pharmacokinetic analysis demonstrates that its serum half-life is almost 24 times that of wild-type hGH. Herein, we provided a promising advancement in the development of site specific PEGylated therapeutic proteins.

Keywords

Human growth hormone PEGylation Site specific modification 

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Notes

Acknowledgements

We gave our sincere thanks to Jessica F. LIU from the School of Medicine at the University of Pennsylvania for reviewing and editing the manuscript.

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Copyright information

© Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Chemistry & Environmental EngineeringChangchun University of Science & TechnologyChangchunP. R. China
  2. 2.Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouP. R. China
  3. 3.University of Chinese Academy of SciencesBeijingP. R. China
  4. 4.Centre for Reproductive Medicine, Centre for Prenatal Diagnosisthe First Hospital of Jilin UniversityChangchunP. R. China
  5. 5.School of Nanotechnology & Chemical EngineeringUniversity of WaterlooWaterlooCanada

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