Thermosensitive PNIPAM-peptide conjugate – Synthesis and aggregation

This paper describes the synthesis of enzymatically cleavable hybrid biomaterial – poly(N-isopropylacrylamide)-pentapeptide conjugate through atom transfer radical polymerization of N-isopropylacrylamide from a resin-loaded peptide macroinitiator. A pentapeptide labeled with a dansyl group (Gly-Arg-Lys-Phe-Gly-dansyl) was synthesized using solid-phase peptide synthesis (SPPS) with the use of Fmoc protected amino acids. An ATRP peptide-based macroinitiator was obtained by the coupling of 2-bromopropionic acid to the N-terminus of peptide molecule. The ATRP of NIPAM was performed in heterogenic conditions using macroinitiator anchored on polystyrene resin. The well-defined PNIPAM-Gly-Arg-Lys-Phe-Gly-dansyl conjugate with an average molar mass of 30,400 g/mol and molar mass dispersity of 1.14 was obtained. The PNIPAM-Gly-Arg-Lys-Phe-Gly-dansyl conjugate underwent a phase transition upon heating in aqueous solution, with the formation of spherical nanoparticles (mesoglobules) with peptide forming the particles’ corona. Tryptic hydrolysis of mesoglobules formed by bioconjugate showed that the presence of Lys or Arg residues in the structure of the conjugate provided a simple route to cleavage peptide fragments from mesoglobules.

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► A thermosensitive PNIPAM-Gly-Arg-Lys-Phe-Gly-dansyl conjugate was synthesised.
► Thermally induced aggregation of bioconjugate to mesoglobules was investigated.
► The peptide linked to the polymer chains formed the outer layer on mesoglobule.
► Peptides located on mesoglobules were fully accessible for enzymatic digestion.