LAUSR

OEGylated polypeptide bearing triethylene glycol monomethylether (OEG3) and poly(ethylene glycol) methyl ether 350 (OEG7) were first prepared by copper-mediated 1,3-dipolar cycloaddition. 1H NMR, FTIR, and GPC results indicated the successful conjugation of oligo(ethylene glycol) (OEG) pendants with high grafting efficiency (≥ 98%). Variable temperature UV–vis spectroscopy revealed a reversible lower critical solution temperature (LCST)-type phase transition of the resulting polypeptides. The LCST-type cloud point temperature (Tcp) in the range of 20–60 °C can be readily tuned by changing the OEG3 and OEG7 composition. Thermo- and pH-responsive polypeptide was prepared by first conjugating of OEG and 6-aldehyde hexyl pendants, then crosslinking in the presence of 1,6-hexanediamine, yielding OEGylated polypeptide bearing pH-labile imine bonds. The resulting polypeptide showed pH-responsive property and less pronounced thermoresponsive property at high pH values (i.e., ≥ 6.15) and noticeable thermo- and pH- dual responsive properties at low pH values (i.e., ≤ 5.80). Graphical abstract We developed a new type of pH- and thermo-responsive OEGylated polypeptides containing imine bonds. The polypeptides are able to show pH-responsive property and less pronounced thermoresponsive property at high pH values and noticeable thermo- and pH- dual responsive properties at low pH values. We developed a new type of pH- and thermo-responsive OEGylated polypeptides containing imine bonds. The polypeptides are able to show pH-responsive property and less pronounced thermoresponsive property at high pH values and noticeable thermo- and pH- dual responsive properties at low pH values.