Synthesis of Poly(Asparagine-co-Phenylalanine) Copolymers, Analogy with Thermosensitive Poly(Acrylamide-co-Styrene) Copolymers and Formation of PEGylated Nanoparticles

Amaury Bossion (1) , Julien Nicolas (1)

1 IGPS - Institut Galien Paris-Saclay

We presented optimized synthetic pathways to high purity L-phenylalanine (Phe) and Lasparagine (Asn) derived N-carboxyanhydrides (NCA) in one-pot processes and in a highly reproducible manner. Ring-opening homopolymerizations of Asn-NCA and Phe-NCA were successfully achieved together with their copolymerization in an attempt to mimic upper critical solution temperature (UCST) vinylic poly(acrylamide-co-styrene) (P(Aam-coSt)) copolymers. Poly(asparagine-co-phenylalanine) (P(Asn-co-Phe)) copolypeptides of different Asn-to-Phe ratio were prepared and their thermoresponsive behavior was investigated in aqueous solution. Unfortunately, polymer aggregation imparted by strong hydrophobic interactions favored due to presence of -sheet structures prevented achieving thermosensitive response in aqueous media in the 50-62°C range conversely to its vinylic counterpart. However, by taking advantage of those strong hydrophobic interactions, PEG-b-PAsn and PEG-b-PPhe diblock copolymers were prepared from amino-PEG initiators and PEG-b-PAsn was successfully formulated into PEGylated nanoparticles of ~270 nm.

Mots clés: N-carboxyanhydride; Asparagine; Phenylalanine; Polypeptide; Nanoparticles; UCST

Domaines: Chimie

Amaury Bossion, Julien Nicolas. Synthesis of Poly(Asparagine-co-Phenylalanine) Copolymers, Analogy with Thermosensitive Poly(Acrylamide-co-Styrene) Copolymers and Formation of PEGylated Nanoparticles. European Polymer Journal, 2020, 140, pp.110033. ⟨10.1016/j.eurpolymj.2020.110033⟩. ⟨hal-03154522⟩