Synthesis, Characterization, and thermoresponsive properties of Helical Polypeptides Derivatized from Poly(γ−4‐(3‐chloropropoxycarbonyl)benzyl‐_L‐glutamate)

Abstract

A series of side-chain-functionalized a-helical polypeptides, i.e., poly (c-4-(3-chloropropoxycarbonyl)benzyl-L -glutamate) (6) have been prepared from n-butylamine initiated ring-opening polymerization (ROP) of c-4-(3-chloropropoxycarbonyl)benzyl-L -glutamic acid-based N-carboxyanhydride. Polypeptides bearing oligo-ethylene-glycol (OEG) groups or 1-butylimidazolium salts were prepared from 6 via coppermediated [213] alkyne-azide 1,3-dipolar cycloaddition or nuleophilic substitution, respectively. CD and FTIR analysis revealed that the polymers adopt a-helical conformations both in solution and the solid state. Polymers bearing OEG (m 5 3) side-chains showed reversible LCST-type phase transition behaviors in water while polymers bearing 1-butylimidazolium and I 2 counter-anions exhibited reversible UCST-type transitions in water. Variable-temperature UV-vis analysis revealed that the phase transition temperatures (T pt s) were dependent on the mainchain length and polymeric concentration.

Synthesis and UCST-type phase behavior of OEGylated poly(γ-benzyl-l-glutamate) in organic media

“…However, they cannot dissolve in DI H 2 O, which is different from the reported polypeptides with OEG pendants that showed LCST‐type phase behaviors in aqueous solutions . OEGylated poly(γ‐benzyl‐ l ‐glutamate)s prepared by 1,3‐dipolar cycloaddition showed LCST‐type phase behaviors when the degree of polymerizaiton of OEG was 3 (i.e., m = 3) while 5b samples showed poor water solubility likely because of the hydrophilicity of 1,3,4‐triazole rings in the former samples. It is interesting to observe that 5a and 5b samples showed an UCST‐type phase behaviors in a variety of alcoholic solvents, including methanol [Fig.…”

“…They have gained increasing attention due to their significant potential application as biomedical materials (e.g., nanoparticles or hydrogels with controlled drug release) . Very recently, we have demonstrated that OEGylated poly(γ‐benzyl‐ l ‐glutamate)s (i.e., PBLG‐OEG 2/3 ) prepared in an eight‐step synthetic route (e.g., ROP and 1,3‐dipolar cycloaddition) showed UCST‐type phase behavior in water, methanol, and ethanol depending on the main‐chain and side‐chain lengths . We reasoned that the α‐helical poly(γ‐benzyl‐ l ‐glutamate) main‐chain and the length of main‐/side‐chains played an important role in the thermoresponsive properties in organic media.…”

Controlled metal‐free polymerization toward well‐defined thermoresponsive polypeptides by polymerization at low temperature

“…In the typical GPC chromatograms (Fig. 5), an obvious peak shift can be observed by comparing PMSELG 20 with PMSELG 20 -g-OEG 4 A 5 and PMSELG 20 -g-OEG 4 A 15 , suggesting an increase of molecular weight after grafting OEGA. In addition, the PDI of the obtained graft polypeptides was relatively low (M w /M n 5 1.2-1.3) and the GPC trace was symmetric, which indicated OEGA was successfully grafted from the polyglutamate backbone in a highly controlled manner by RAFT polymerization.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Particularly interesting are thermoresponsive polypeptides, which can change their conformation or secondary structure in response to the temperature change. [20][21][22][23][24] Many studies have been done to prepare thermoresponsive polypeptides in recent years. [25][26][27][28][29] Li employed direct ringopening polymerization (ROP) of pegylated-L-glutamic acid N-carboxyanhydride (NCA) with different oligo(ethylene glycol) (OEG) lengths to synthesize the first thermoresponsive polypeptide in 2011.…”

Synthesis and UCST-type phase behaviors of OEGylated random copolypeptides in alcoholic solvents

“…Recently, stimuli‐responsive polypeptides with responsiveness to pH, temperature, light, oxidation, and gas have gained increased attention for their great potential as smart biomaterials . While thermoresponsive polypeptides with LCSTs have been intensively studied, thermoresponsive polypeptides with UCSTs have been less investigated . For example, polypeptides with ionic liquid pendants (e.g., imidazolium or pyridinium) showed UCST‐type phase behaviors in aqueous solutions.…”