Synthesis and LCST-type phase behavior of water-soluble polypeptide with Y-shaped and charged side-chains

Abstract

Water-soluble thermoresponsive poly(γ-4-methylbenzyl-L-glutamate) bearing Y-shaped (i.e., oligo-ethylene-glycol and alkyl groups, such as 1-butyl, 1-hexyl, or 1-dodecyl) and triazolium tetrafluoroborate side-chains (PMBLG-OEG₇/C_m-BF₄, m = 4, 6, and 12) have been prepared by nucleophilic substitution of poly(γ-4-methylbenzyl-L-glutamate)-oligo-ethylene-glycol conjugates (PMBLG-OEG₇) and various 1-alkyl bromide and ion-exchange reactions of triazolium bromide and NaBF₄. Poly(γ-4-chloromethylbenzyl-L-glutamate) (PCMBLG) was derivatized into poly(γ-4-azidomethylbenzyl-L-glutamate) (PAMBLG), followed by reaction with propargyl functionalized polyethylene glycol monomethylether 350 (Pr-OEG₇) via a copper-mediated 1,3-dipolar cycloaddition to yield PMBLG-OEG₇. PMBLG-OEG₇/C_m-BF₄, m = 4, 6, and 12) adopted an α-helical conformation and showed lower critical solution temperature (LCST)-type phase behaviors in aqueous solutions. The cloud point temperature (T_cp) was significantly decreased with an increase in polymer concentration and salt (e.g., NaBF₄) concentration. Elongating the alkyl chain length can further decrease the T_cp.