Amphiphilic Nucleobase-Containing Polypeptide Copolymers—Synthesis and Self-Assembly

Michel Nguyen (1) , Khalid Ferji (2) , Sébastien Lecommandoux (3, 4) , Colin Bonduelle (1, 3, 4)

1 LCC - Laboratoire de chimie de coordination
2 LCPM - Laboratoire de Chimie Physique Macromoléculaire
3 LCPO - Laboratoire de Chimie des Polymères Organiques
4 Team 3 LCPO : Polymer Self-Assembly & Life Sciences

Nucleobase-containing polymers are an emerging class of building blocks for the self-assembly of nanoobjects with promising applications in nanomedicine and biology. Here we present a macromolecular engineering approach to design nucleobase-containing polypeptide polymers incorporating thymine that further self-assemble in nanomaterials. Diblock and triblock copolypeptide polymers were prepared using sequential ring-opening polymerization of γ-Benzyl-l-glutamate N-carboxyanhydride (BLG-NCA) and γ-Propargyl-l-glutamate N-carboxyanhydride (PLG-NCA), followed by an efficient copper(I)-catalyzed azide alkyne cycloaddition (CuAAc) functionalization with thymidine monophosphate. Resulting amphiphilic copolymers were able to spontaneously form nanoobjects in aqueous solutions avoiding a pre-solubilization step with an organic solvent. Upon self-assembly, light scattering measurements and transmission electron microscopy (TEM) revealed the impact of the architecture (diblock versus triblock) on the morphology of the resulted nanoassemblies. Interestingly, the nucleobase-containing nanoobjects displayed free thymine units in the shell that were found available for further DNA-binding.

Mots clés: sequential ring-opening polymerization; amphiphilic polypeptide; nucleobase; spontaneous self-assembly; DNA binding

Domaines: Polymères; Matière Molle [cond-mat.soft]; Biochimie, Biologie Moléculaire

Michel Nguyen, Khalid Ferji, Sébastien Lecommandoux, Colin Bonduelle. Amphiphilic Nucleobase-Containing Polypeptide Copolymers—Synthesis and Self-Assembly. Polymers, 2020, 12 (6), pp.1357. ⟨10.3390/polym12061357⟩. ⟨hal-02876032⟩