Reversible Bioconjugation: Biodegradable Poly(phosphate)-Protein Conjugates

Tobias Steinbach, Greta Becker, Alina Spiegel, Tamiris Figueiredo, Daniela Russo, Frederik R. Wurm*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Scopus)


Protein-polymer conjugates are widely used to improve the pharmacokinetic properties of therapeutic proteins. Commercially available conjugates employ poly(ethylene glycol) (PEG) as the protective polymer; however, PEG has a number of shortcomings, including non-biodegradability and immunogenicity, that call for the development of alternatives. Here, the synthesis of biodegradable poly(phosphate), that is, poly(ethyl ethylene phosphate) (PEEP), by organo-catalyzed anionic ring-opening polymerization exhibiting dispersity values Ð < 1.3 is reported. Polymers with molecular weights between 2000 and 33 200 g mol−1 are then ω-functionalized with a succinimidyl carbonate group and subsequently conjugated to model proteins. These are the first conjugates based on polyphosphates which degraded upon exposure to phosphodiesterase. As is the case for PEGylated therapeutics, residual in vitro activity of the PPEylated conjugates depends on the extent of protein modification. These results suggest that PEEP exhibits the desired properties of a biopolymer for use in next generation, fully degradable drug delivery systems. (Figure presented.).

Original languageEnglish
Article number1600377
JournalMacromolecular bioscience
Issue number10
Publication statusPublished - Oct 2017
Externally publishedYes


  • biodegradable polymer
  • PEGylation
  • poly(phosphoester)s
  • protein-polymer conjugates


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