Chapter 1:Synthetic Aspects of Peptide– and Protein–Polymer Conjugates in the Post-click Era

Biomacromolecules offer complex and precise functions embedded in their monomer sequence such as enzymatic activity or specific interactions towards other molecules. Their informational content and capability to organize in higher ordered structures is superior to those of synthetic molecules. In comparison, synthetic polymers are easy to access even at large production scales and they are chemically more diverse. Solubilization, shielding against enzymatic degradation to more advanced functions like switchability or protein mimicry, etc., are accessible through the world of polymer chemistry. Bio-inspired hybrid materials consisting of peptides or proteins and synthetic polymers thereby combine the properties of both molecules to give rise to a new class of materials with unique characteristics and performance. To obtain well-defined bioconjugate materials, high yielding and site-specific as well as biorthogonal ligation techniques are mandatory. Since the first attempts of protein PEGylation in the 1970s and the concept of “click” chemistry arising in 2001, continuous progress in the field of peptide– and protein–polymer conjugate preparation has been gained. Herein, we provide an overview on ligation techniques to prepare functional bioconjugates published in the last decade, also referred to as “post-click” methods. Furthermore, chemoenzymatic approaches and biotransformation reactions used in peptide or protein modification, as well as highly site-specific and efficient reactions originated in synthetic macromolecular chemistry, which could potentially be adapted for bioconjugation, are presented. Finally, future perspectives for the preparation and application of bioconjugates at the interface between biology and synthetic materials are given.