Peptide/protein-polymer conjugates: synthetic strategies and design concepts.
This feature article provides a compilation of tools available for preparing well-defined peptide/protein-polymer conjugates, which are defined as hybrid constructs combining (i) a defined number of peptide/protein segments with uniform chain lengths and defined monomer sequences (primary structure) with (ii) a defined number of synthetic polymer chains. The first section describes methods for post-translational, or direct, introduction of chemoselective handles onto natural or synthetic peptides/proteins. Addressed topics include the residue- and/or site-specific modification of peptides/proteins at Arg, Asp, Cys, Gln, Glu, Gly, His, Lys, Met, Phe, Ser, Thr, Trp, Tyr and Val residues and methods for producing peptides/proteins containing non-canonical amino acids by peptide synthesis and protein engineering. In the second section, methods for introducing chemoselective groups onto the side-chain or chain-end of synthetic polymers produced by radical, anionic, cationic, metathesis and ring-opening polymerization are described. The final section discusses convergent and divergent strategies for covalently assembling polymers and peptides/proteins. An overview of the use of chemoselective reactions such as Heck, Sonogashira and Suzuki coupling, Diels-Alder cycloaddition, Click chemistry, Staudinger ligation, Michael's addition, reductive alkylation and oxime/hydrazone chemistry for the convergent synthesis of peptide/protein-polymer conjugates is given. Divergent approaches for preparing peptide/protein-polymer conjugates which are discussed include peptide synthesis from synthetic polymer supports, polymerization from peptide/protein macroinitiators or chain transfer agents and the polymerization of peptide side-chain monomers.
Gauthier
Marc A
MA
Ecole Polytechnique Fédérale de Lausanne, Institut des Matériaux, Laboratoire des Polymères, Bâtiment MXD, Station 12, CH-1015, Lausanne, Switzerland.
Klok
Harm-Anton
HA
D000478:Alkylation; D000595:Amino Acid Sequence; D006835:Hydrazones / Q000737:chemistry; D008969:Molecular Sequence Data; D010091:Oximes / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis*; D011487:Protein Conformation; D011506:Proteins / Q000138:chemical synthesis*
D006835:Hydrazones; D010091:Oximes; D010446:Peptide Fragments; D010455:Peptides; D011506:Proteins