Polymer Synthesis with Polypeptide Macroinitiators

In most reports, the peptide-polymer-conjugates are prepared by using a polymeric macroinitiator for the polymerization of the polypeptide however, the sequence can also be reversed. Polypeptides can be prepared and used as macroinitiators for a polymerization. Particularly suited for this approach are controlled polymerization techniques because they usually allow good end-group control and adjustment of the molecular weight and the molecular weight distribution of the polymer block. There are different mechanisms for a controlled radical polymerization that can be used for this purpose stable free-radical polymerization (SFRP), ATRP, and reversible addition fragmentation chain transfer (RAFT) polymerization. 

The technique was taken a step further by crossUnking the block copolymers with divinylbenzene (DVB) to form nanoparticles with a crosslinked PS core and PS-Z -PBLG arms (see Fig. 8). A clear effect of the block length ratio and the amount of crosslinker in the process was observed. While gel formation occurred even at low block copolymer-to-crosslinker ratios for shorter block copolymers, individual core-shell particles were accessible with longer block copolymers. By debenzylation, PGA blocks are produced and the nanoparticles become water-soluble and pH-sensitive [81]. 

The combination of amine-initiated NCA polymerization and NMP was also used to prepare amphiphilic peptide-polymer conjugates having copolymers of L glutamic acid and L-alanine as polypeptide and poly(n-butyl aciylate) or PS as polymer block. Micelles and vesicles were prepared from these block copolymers and the effects of peptidases on these particles were tested. It is possible to tune the enzymatic degradation by altering the amino acid composition in the polypeptide block [77]. 

Homopolypeptides prepared by a NCA polymerization can also be used with ATRP. Qiu et al. have used amine-terminated dendtimers for an amine-initiated 

NCA polymerization. Subsequently, the N-terminus of the polypeptide chains was converted into an ATRP initiator by reaction with a-bromo isobutyric acid and used to polymerize d gluconoamidoethyl methacrylate. In this way, star-shaped polypeptide/glycopolymer biohybrids with controlled molecular weights and low polydispersities were synthesized [98]. 

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Research on the synthesis of polypeptide hybrid diblock copolymers began in the mid-1970s (Yamashita et al., 1975). Advances in polymer synthesis, culminating in the development of controlled/living polymerization techniques and click chemistry (Sumerlin and Vogt, 2010), in combination with the living ROP of NCAs, allowed for the preparation not only of simple diblock but also of a wide variety of multiblock Chimeras. In this section we will describe the materials synthesized according to the macroinitiators used for the ROP of the NCAs amino-and transition-metal complexes. 

Another type of polypeptide-containing block copolymer, amphiliphilic rod-coil diblock copolymers such as poly (/V-triflu-oroacetyl-L-lysine)-/>-sarcosine) (Kt - Sa), were also synthesized and characterized by Gallot and coworkers [47]. The hydrophobic rod block poly(A-trifluoroacetyl-L-ly-sine) (Kt) was prepared by polymerization of Kt-NCA using A-hexylamine as the initiator. After fractionation using DMF (good solvent)/water (nonsolvent), the narrowly dispersed polymer (Kt) was then used as macroinitiator to initiate polymerization of the second monomer (Sa-NCA) to afford the hydrophilic block. Final elimination of Kt and Sa homopolymers were performed by precipitation with acetone and water respectively. The synthesis of Kt-Sa diblock copolymer is shown in Scheme 3. 

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