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Copper, one of the most important metal elements, has been a new favorite in research areas. However, the Cu2+ detection strategy with high-efficient and biocompatibility maintains importance. Here, we made effort to develop a new sensor with above advantages for Cu2+ detection. By virtue of rich coordination sites (amidogen and carboxyl) and fluorescence property of aromatic amino acids that which are also essential for living organism, monomers and combinations of them are designed to interact with Cu2+, attractively, the short peptide of tryptophane–phenylalanine (Trp–Phe) held stronger fluorescence emission and displayed much more significant response to Cu2+ than other molecules; thus, Trp–Phe was screened as a new fluorescent sensor for Cu2+ detection. It had a rapid response to the target ion via a coordination-mediated PET effect, the signal change reached the maximum within 10 s; cell proliferation experiments verified that the screened peptide had excellent biocompatibility, implying that it had great environment-friendliness and convenience for practical application in Cu2+ detection; high selectivity and a wide linear detection range from 10 to 1500 nM were achieved, with a lowest detectable concentration of 10 nM, which are superior to conventional optical strategies; through analysis of real water samples, good recoveries and consistencies with classical inductively coupled plasma mass spectrometry indicated that this strategy had promising potential for practical application, especially significant for Cu2+ detection in drinking water; and in addition, Cu2+ antidotes identification was successfully carried out, implying useful contribution to medical therapy and sewage treatment.

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