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Chemical Synthesis of Interleukin‐2 and Disulfide Stabilizing Analogues


Murar, Claudia E; Ninomiya, Mamiko; Shimura, Satomi; Karakus, Ufuk; Boyman, Onur; Bode, Jeffrey W (2020). Chemical Synthesis of Interleukin‐2 and Disulfide Stabilizing Analogues. Angewandte Chemie Internationale Edition, 59(22):8425-8429.

Abstract

Chemical protein synthesis allows the construction of well-defined structural variations and facilitates the development of deeper understanding of protein structure-function relationships and new protein engineering strategies. Herein, we report the chemical synthesis of interleukin-2 (IL-2) variants on a multimilligram scale and the formation of non-natural disulfide mimetics that improve stability against reduction. The synthesis was accomplished by convergent KAHA ligations; the acidic conditions of KAHA ligation proved to be valuable for the solubilization of the hydrophobic segments of IL-2. The bioactivity of the synthetic IL-2 and its analogues were shown to be equipotent to recombinant IL-2 and exhibit improved stability against reducing agents.

Abstract

Chemical protein synthesis allows the construction of well-defined structural variations and facilitates the development of deeper understanding of protein structure-function relationships and new protein engineering strategies. Herein, we report the chemical synthesis of interleukin-2 (IL-2) variants on a multimilligram scale and the formation of non-natural disulfide mimetics that improve stability against reduction. The synthesis was accomplished by convergent KAHA ligations; the acidic conditions of KAHA ligation proved to be valuable for the solubilization of the hydrophobic segments of IL-2. The bioactivity of the synthetic IL-2 and its analogues were shown to be equipotent to recombinant IL-2 and exhibit improved stability against reducing agents.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Immunology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Physical Sciences > Catalysis
Physical Sciences > General Chemistry
Uncontrolled Keywords:General Chemistry, Catalysis
Language:English
Date:25 May 2020
Deposited On:15 Feb 2021 13:06
Last Modified:16 Feb 2021 21:02
Publisher:Wiley-VCH Verlag
ISSN:1433-7851
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/anie.201916053
PubMed ID:32032465
Project Information:
  • : FunderSNSF
  • : Grant ID200020_169451
  • : Project TitleProtein Synthesis with Chemoselective Ligations
  • : FunderSNSF
  • : Grant ID200020_150073
  • : Project TitleChemoselective Protein Ligation

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