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Polymer conjugation to proteins has been widely used to improve or expand protein properties. However, polymer conjugation to random sites of a target protein often led to a significant loss of critical protein properties. In order to overcome this, polymer conjugation to specific sites of a protein was developed using the site-specific introduction of non-natural amino acids and bioorthogonal chemistries. This review summarizes the recent advances in bioorthogonal chemistries. As the repertoire of bioorthogonal chemistries available for polymer conjugation is expanding, the site-specific polymer conjugation technique would be a valuable platform technique to design novel protein–polymer conjugates.

Graphical abstract: Expansion of bioorthogonal chemistries towards site-specific polymer–protein conjugation

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