A synthetic strategy to couple selectively an ionic complementary thiol modified octapeptide, that is able to gel at low temperature, to the thermoresponsive polymer poly(Nisopropylacrylamide) (pNIPAAm) with controlled molecular weight and narrow polydispersity is described. The polymer was synthesized by atom transfer radical polymerization (ATRP) affording halogen functionalized chain ends. This allowed subsequent coupling to a thiol terminated ionic complementary octapeptide via nucleophile substitution. Results indicated that the peptide was covalently attached to the polymer and that both the coil-globule phase transition of pNIPAAm and the gelation properties of the peptide were retained in the conjugated product. This method provides a versatile route for the synthesis of a range of bioconjugate materials with controlled architecture and dual self-assembling and thermoresponsive behavior.
INTRODUCTIONThe increasing utility of polymer-protein conjugates in medicine, biotechnology and nanotechnology has driven the need for generating homogeneous and well defined biohybrid materials. Such bio-conjugate materials combine the controlled mechanical, thermal and electronic properties of synthetic polymers with the functionality and bioactivity of designed bioactive groups, such as peptides, making them attractive candidates for biomedical applications such as drug delivery and cell culture scaffold. Numerous synthetic routes have been explored to prepare such conjugates. One synthetic pathway includes the solid phase synthesis of peptides where the last coupling step introduced a polymer initiator which is subsequently used to grow polymer via radical polymerization 1 while still attached on the resin. An alternative route relies on the attachment of amine terminated polymers to the solid resin with subsequent solid phase peptide synthesis 2 . The main drawback of both these methodologies is their exclusiveness to a specific polymer and peptide.Recently, we reported a novel, selective synthesis route for the preparation of polymerpeptide conjugates using a modified peptide with a thiol terminus as a transfer agent in the free radical polymerization of pNIPAAm 3 . Due to the inherent lack of control of free radical polymerization, conjugates with high molecular weight and broad molecular weight distribution were obtained. To allow the synthesis of conjugates with well-defined architecture, polymer length and controlled functionalities and properties, living polymerization has been introduced. Such polymerizations -cationic, anionic, coordination, ring-opening and radical polymerizations -which proceed in the absence of irreversible chain transfers and chain terminations, have been successfully applied to numerous monomers. Of particular interest is atom transfer radical polymerization (ATRP) 4 which, in addition to allowing for the controlled synthesis of polymers with narrow polydispersities, has the inherent ability to yield halogen chain end functionalized polymers. This offers the possibility of further modifi...