Polymers with attached functional groups may be prepared directly by polymerization of functional monomers (i.e., monomers appended with the functional groups). However, some functional monomers may not be directly polymerized by any polymerization process or may not polymerize in the desired manner. In such case, post-polymerization modification, such as the “grafting onto” method, is necessary to prepare a desired polymer. For example, “click chemistry” has been used in a wide variety of polymer applications including functionalization of polymers with small molecules, formation of diblock polymers, formation of new dendrimers, formation of macromonomers, crosslinking of micelles, and the “grafting onto” method of forming molecular brushes (see, for example, U.S. Patent Application Publication No. 2007/0244265 to Matyjaszewski, which is the U.S. national stage of International Patent Application No. PCT/US05/07264, and which is hereby incorporated by reference in its entirety).
Synthetic polypeptides with attached functional groups have been used to prepare “tailored polypeptides.” Tailored polypeptides have attracted significant interest for hybrid polymer drug and gene delivery systems, tissue engineering, and polypeptide adhesives. Synthetic polypeptides have several features that make them very attractive for biological applications including low toxicity, biodegradability, predictable structures, and well-controlled dimensions. Synthetic polypeptides have previously been synthesized using a well-studied N-carboxyanhydride (NCA) ring-opening polymerization (ROP) which utilizes a wide variety of monomers containing various functional groups. In particular, carboxylic acid (e.g., glutamate and aspartate) and amino (e.g., lysine) groups of the amino acids have been used to add chemical moieties such as pharmaceutical drugs and molecules that dictate hydrophobicity or pH responsiveness. However, functionalization of polypeptides synthesized by NCA ROP has several limitations. Because of the nature of the polymerization, the type of monomer that can be used is limited to NCAs with alkane end groups or NCAs where the functional group is protected. When creating polypeptides with functional carboxylic acid or amino groups, a three step process is often required: (1) polymerization with the protected functional group, (2) the deprotection of the functional group, and (3) the functionalization. In addition, if a high degree of functionalization is required, the added chemical moieties are limited to small molecules and low molecular weight oligomers. In addition, the addition of polymeric side chains using a “grafting onto” method at a high grafting density has not been attainable; in fact, the addition of polymeric side chains using a “grafting onto” method at a high grafting density (i.e., above 50%) has not been attainable.