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

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/Cm-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/Cm-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 (Tcp) was significantly decreased with an increase in polymer concentration and salt (e.g., NaBF4) concentration. Elongating the alkyl chain length can further decrease the Tcp.