Polypeptide hybrid block copolymers

Osada, K. and Kataoka, K Drug and Gene Delivery Based on Supramolecular Assembly of PEG-Polypeptide Hybrid Block Copolymers. Vol. 202, pp. 113-154. 

Despite the drawbacks of this method, it has been used to prepare a tremendous number of polypeptide hybrid block copolymers (Table 1), and when carefully executed provides reasonably well-defined samples. Synthetic polymer domains have been prepared by addition polymerization of conventional vinyl monomers, such as styrene and butadiene, as well as by ringopening polymerization in the cases of ethylene oxide and e-caprolactone. The generality of this approach allows NCA polymerization off of virtually any primary amine functionality, which was exploited in the preparation of star block copolymers by polymerization of sarcosine NCA from an amine-terminated trimethyleneimine dendritic core [37]. In most examples, the polypeptide domain was based on derivatives of either lysine or glutamate, since these form a-helical polypeptides with good solubility characteristics. These residues are also desirable since, when deprotected, they give polypep-... 

Table 1 Examples of polypeptide hybrid block copolymers prepared from macromolecular amine initiators [8,9]. Block architectures are primarily AB diblocks or ABA triblocks, where the polypeptide segment is the A domain, and the macroinitiator is the B domain ...

The synthesis of polypeptide hybrid block copolymers is an area that has been under study for three decades. Initially, this field suffered from limitations in the synthesis of the polypeptide components that required excessive sample purification and fractionation to obtain well-defined copolymers. In recent years, vast improvements in NCA polymerizations now allow the synthesis of hybrid block copolymers of controlled dimensions (molecular weight, sequence, composition, and molecular weight distribution). Such well-defined materials will greatly assist in the identification of new self-assembled structures possible using ordered polypeptide segments, as well as yield new materials with a wide range of tunable properties. 

Besides the polypeptide hybrid block copolymers described earlier, there exist a few examples of purely peptide-based amphiphiles and block/random copolymers (copolypeptides) (Fig. 10). In the latter case, both the core and corona of aggregates consist of a polypeptide. Any of the studies reported so far dealt with aggregation in aqueous media. 

The linear polypeptide hybrid block copolymers and block copolypeptides reported to form vesicles in aqueous solution are listed in Fig. 1. 

Osada K, Kataoka K (2006) Drug and gene delivery based on supramolecular assembly of PEG-polypeptide hybrid block copolymers. Adv Polym Sci 202 113-153... 

Polymer-polypeptide hybrid block copolymers are able to self-assemble either in bulk (microphase separation) or in selective solvents (micellization), like conventional block copolymers, and in addition are organized within the microphases into a-helix or j5-sheet... 

Zero-valent metal complexes cannot be used directly for the synthesis of polypeptide hybrid block copolymers. However, N° -allyloxycarbonyl-amino acid allyl amides can be used as universal precursors for the amido-amidate nickelacycle initiators (Scheme 15.8). As shown in Scheme 15.8, the N°"-allyloxycarbonyl-amino acid derivatives may undergo tandem oxidative additions to nickel(O) giving the nickelacycle initiators. This method was initially employed for the synthesis of block copolypeptides and was then expanded by Deming and coworkers to a variety of hybrid structures. 

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