Design and synthesis of amphiphilic alternating peptides with lower critical solution temperature behaviors

Amphiphilic peptides consisting of an alternating binary pattern of repeating hydrophilic and hydrophobic units were synthesized via polymerization exploiting Ugi’s four-component condensation reaction (Ugi’s 4CC) as the fundamental polymerization reaction. We performed turbidity measurements of the aqueous polymer solutions at various temperatures. The results showed that the structural effects of the alternating peptides had the following impacts on thermoresponsiveness: (i) amphiphilic alternating peptides with repeating hydrophilic and hydrophobic units tended to adopt upper critical solution temperature (UCST) behavior; and (ii) when the hydrophobes in the polymer were large enough for intrachain hydrophobic interactions, the polymer displayed lower critical solution temperature (LCST) behavior. In addition, we prepared thermoresponsive hydrogels comprising poly(N,N-dimethylacrylamide) as the main chain with alternating peptide skeletons as the cross-linking points. The swellability of the hydrogels in water was clearly dependent on temperature, indicating that the thermal transition of the alternating peptides as the cross-linking points led to the hydrogel volume change. Alternating peptides with LCST behavior may be useful for creating peptide-based smart materials in the future.