Facile synthesis of block copolypeptides of defined architecture

Many natural polymeric materials (particularly structural proteins) display a hierarchy of structure over several length scales. Block copolymers are able to self-assemble into ordered nanostructures(1,2), but the random-coiled nature of their polymer chains usually suppresses any further levels of organization. The use of components with regular structures, such as rigid-rod polymers, can increase the extent of spatial organization in self-assembling materials(3). But the synthesis of such polymeric components typically involves complicated reaction steps that are not suitable for large-scale production. Proteins form hierarchically organized structures in which the fundamental motifs are generally alpha-helical coils and beta-sheets(4). Attempts to synthesize polypeptides with well-defined amino-acid sequences, which might adopt similar organized structures, have been plagued by unwanted side reactions(5) that give rise to products with a wide range of molecular weights(6-10), hampering the formation of well-defined peptide block copolymers(11-17). Here I describe a polymerization strategy that overcomes these difficulties by using organonickel initiators which suppress chain-transfer and termination side reactions. This approach allows the facile synthesis of block copolypeptides with well-defined sequences, which might provide new peptide-based biomaterials with potential applications in tissue engineering, drug delivery and biomimetic composite formation.