1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 z Biological Chemistry & Chemical Biology Mercuric Ion Sensing by an Overlapping b-turn Containing Peptide Kalpana Tomar,* [a] Satyendra Soni,* [a] Pratibha Bhadauriya, [b] Rashmi Parihar, [b] Subramaniam Ganesh,* [b] Nisanth N. Nair,* [a] and Gurunath Ramanathan* [a] A tetrapeptide containing dehydrophenylalanine residue exhib- its unusual enhanced fluorescence emission intensity for Hg 2 + ions selectively. In vivo studies on HeLa cells revealed that this peptide could be used to study Hg 2 + trafficking in mammalian cells. The results demonstrate that Hg 2 + can interact with sulfurless peptide backbones, if the latter provides the requisite geometry, especially a folded type III/III overlapping beta turn conformation. Mercury exposure has been implicated in several human disorders such as the Minamata disease. [1] Mercury is widely distributed on earth, mostly in the form of its inorganic salts. Its accumulation in humans is principally via food chain and largely as methyl mercury. [2] Indeed, organic forms of mercury are eliminated with greater difficulty in comparison to the inorganic forms. Contamination of the environment by mercury occurs mainly as a result of anthropogenic activities. There is a growing concern to avoid mercury contamination due to its implicated toxicity towards biota. Interaction of mercury with proteins and other organics has been a subject of intense investigations due to the aforementioned reasons. [3] Several studies have focused on interaction of mercury with biological systems wherein these interactions are supposedly mediated through the thiol groups on proteins. [4] Several aromatic amines are orthomercurated and stabilized by weak N….Hg interactions. [5] We chose to incorporate a,b- dehydrophenylalanine (DPhe) to study these interactions as this residue is found in bioactive peptides. [6] DPhe residue induces enhanced resistance to enzymatic degradation. [7] This residue also enables a rich assortment of well-defined secon- dary structural motifs and is found in several natural prod- ucts. [7–8] The achiral nature of DPhe residue allows it to be incorporated in both left and right-handed helical conforma- tions of peptides. The Z isomer is thermodynamically more stable, and has been well studied. [9] Structural studies of dehydropeptides have shown that the DPhe residue is a strong inducer of a-bends in short sequences but prefers 3 10 -helical conformations in longer peptides. [8] Occurrence of b-turns in conformationally restricted DPhe containing peptides and their characteristic i ! i + 3 intramolecular C =O…H À N hydrogen bond in both solution and solid state are well documented. [10] A notable number of DPhe containing peptides of varying length have been reported to possess 3 10 -helical conformations with both right- and left-handedness. [11] The conformational energy calculations indicate that the preference of Aib residue prevails over the preference of DPhe residue in peptides containing both these residues. [12] Herein, we report a tetra peptide Bz- ~ Phe(NPh 2 )-Ala-Leu- Aib-OMe (Figure 1) that selectively senses Hg 2 + ions in the presence of other ions by turn-on fluorescence response; the tetrapeptide is devoid of sulphur atom and employs over- lapping beta turn scaffold to bind mercuric ions. The backbone adopts a folded conformation with over- lapping b-turn of type III/III. While both peptides A and B in [a] K. Tomar, S. Soni, Prof. Dr. N. N. Nair, Prof. Dr. G. Ramanathan Department of Chemistry Indian Institute of Technology Kanpur Kanpur, Uttar Pradesh, INDIA -208016 E-mail: gurunath@iitk.ac.in ktomar@iitk.ac.in sonisatyendra44@gmail.com nnair@iitk.ac.in [b] P. Bhadauriya, Dr. R. Parihar, Prof.Dr. S. Ganesh Department of Biological Sciences and Bioengineering Indian Institute of Technology Kanpur Kanpur, Uttar Pradesh, INDIA -208016 E-mail: pratibhazera@gmail.com rashmip@iitk.ac.in sganesh@iitk.ac.in Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201701058 Figure 1. Structure of the peptide studied. The p-diaminophenyl substitution gives the peptide an inbuilt fluorophore that could be exploited for mercury detection. Communications DOI: 10.1002/slct.201701058 8072 ChemistrySelect 2017, 2, 8072 – 8075  2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim