4.6 Article

Characterization of PEGylated Asparaginase: New Opportunities from NMR Analysis of Large PEGylated Therapeutics

Journal

CHEMISTRY-A EUROPEAN JOURNAL
Volume 25, Issue 8, Pages 1984-1991

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201804488

Keywords

biopharmaceuticals; PEGylation; protein modifications; protein structures; structural biology

Funding

  1. Fondazione Cassa di Risparmio di Firenze, MIUR [PRIN 2012SK7ASN]
  2. COST Action [CA15209]
  3. EC [653706]
  4. University of Florence CERM-TT
  5. Recombinant Proteins JOY-NLAB
  6. FP7 WeNMR [261572]
  7. H2020 West-Life [675858]

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Resonance assignment and structural characterization of pharmacologically relevant proteins promise to improve understanding and safety of these proteins by rational design. However, the PEG coating that is used to evade the immune system also causes these molecules to evade the standard structural biology methodologies. We here demonstrate that it is possible to obtain the resonance assignment and a reliable structural model of large PEGylated proteins through an integrated approach encompassing NMR and X-ray crystallography.

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