A new fluorescent peptidyl chemosensor based on the mercury binding MerP protein with fluorescence resonance energy transfer (FRET) capabilities has been synthesized via Fmoc solid-phase peptide synthesis. The metal chelating unit, which is flanked by the fluorophores tryptophan (donor) and dansyl (acceptor), contains amino acids from MerP's metal binding loop (sequence: dansyl-Gly-Gly-Thr-Leu-Ala-Val-Pro-Gly-Met-Thr-Cys-Ala-Ala-Cys-Pro-Ile-Thr-Val-Lys-Lys-Gly-Gly-Trp-CONH(2)). A FRET enhancement or 'turn-on' response was observed for Hg(2+) as well as for Zn(2+), Cd(2+) and Ag(+) in a pure aqueous solution at pH 7.0. The emission intensity of the acceptor was used to monitor the concentration of these metals ions with detection limits of 280, 6, 103 and 496 microg L(-1), respectively. No response was observed for the other transition, alkali and alkaline earth metals tested. The fluorescent enhancement observed is unique for Hg(2+) since this metal generally quenches fluorescence. The acceptor fluorescence increase resulting from metal binding-induced FRET suggests a sensor that is inherently more sensitive than one based on quenching by the binding event.