OEGylated polypeptide bearing Y-Shaped pendants with a LCST close to body temperature: Synthesis and thermoresponsive properties

The understanding of molecular structure and thermoresponsive property relationships and development of water-soluble thermoresponsive polymers with tunable cloud point temperatures (T(cp)s) are crucial toward versatile practical uses. Herein, OEGylated polypeptides bearing Y-shaped pendants, namely poly(gamma-4-(propoxycarbonyl)benzyl-L-glutamate)-oligo(ethylene glycol) conjugates (8-OEGx, x = 2, 3) were synthesized by the combination of ring-opening polymerization of gamma-4-(allyloxycarbonyl)benzyl-L-glutamic acid based N-carboxyanhydride (4) and subsequent side-chain modifications, including bromination of poly(gamma-4-(allyloxycarbonyl) benzyl-L-glutamate) (5), nucleophilic substitution of 5 in the presence of NaN3, and subsequent copper-mediated 1,3-dipolar cycloaddition. Both H-1 NMR and FTIR analysis confirmed the molecular structures of the intermediates and 8-OEGx. In aqueous solutions, 8-OEGx samples showed reversible lower critical solution temperature (LCST)-type phase transitions in broad polymer concentration range (0-30 mg.mL(-1)). Variable-temperature UV-vis spectroscopy results revealed that the LCST-type T-cp of 8-OEG(2) at high polymer concentrations (e.g., >= 10 mg.mL(-1)) was in the range of 37.5-42.5 degrees C. 8-OEG(2) showed a remarkable increase of hydrophilicity than PBLG-OEG(4) with the same amount of OEG units as well as linear shaped pendants. The T-cp of OEGylated polypeptides increased by addition of NaI, yet it decreased upon addition of NaCl, NaBr, or KCl, which obeys the Hofmeister effect.