Inspired by biological nanochannels, a novel cyclic 3’,5’-adenosine monophosphate (cAMP)–regulated artificial nanochannel based on a tripeptide Arg-Thr-Ala (RTA) design is developed. Highly specific binding between the tripeptide and cAMP triggers an obvious conformational transition of a smart polymer chain from a contracted state to a swollen one, which leads to a dynamic modulation of the gating behaviours of the nanochannels.