New polymer-peptide conjugates, NIPAM-PEP and NIPAM-PEPEP, were designed and synthesized. These graft-type polymers contained a substrate peptide of protein kinase A (PKA), which forms one of the most important intracellular signals in cellular signal transduction. The NIPAM-PEP containing the N-isopropylacrylamide unit and the substrate peptide unit raised its lower critical solution temperature (LCST) from 36.7 to 40 °C in response to phosphorylation by activated PKA. The NIPAM-PEPEP containing another poly(ethylene glycol) unit formed a polymer micelle-type particle above LCST. This particle disintegrated in response to phosphorylation by activated PKA. Dansylaniline, which was encapsulated in the hydrophobic core of the particle, tended to be released with the particle disintegration occurring in response to the PKA signal. NIPAM-PEPEP, which is the first example of a polymer-peptide conjugate responding to an intracellular signal, offers the possibility of a novel, intelligent drug capsule communicating with cells to release its pharmacological activity.
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