Abstract: Four tetrapeptides containing dehydrophenylalanine residue have been shown to adopt a folded overlapping beta turn conformation. Crystallographic analysis of these tetrapeptides: Bz-∆Phe-Ala-Leu-Aib-OMe (peptide A), Bz-∆Phe(OCH3)-Ala-Leu-Aib-OMe (peptide B), Bz-∆Phe(1,4-dioxin)-Ala-Leu-Aib-OMe (peptide C), Bz-∆Phe(NPh2)-Ala-Leu-Aib-OMe (peptide D) reveals that they adopt a type III/III overlapping turns in all peptides.  Modulation of the dehydrophenylalanine side chain to improve fluorescence in these peptides was exploited for the detection of Hg2+ ions using peptides D. Further, in vivo studies on HeLA cells revealed that peptide D could be used to study Hg2+ trafficking in mammalian cells.    

Mercury exposure has been implicated in several human disorders.  While mercury is widely dispersed mostly as inorganic salts on earth, its accumulation and magnification in humans is principally via the food chain and mostly as methyl mercury.1 Indeed organic forms of mercury are eliminated with greater difficulty in comparison to the inorganic forms. Mercury contamination of the environment mainly occurs as a result of anthropogenic activities and is increasingly considered avoidable due to its implicated toxicity towards biota.
Interaction of mercury with proteins and other organics has been a subject of intense investigation and debate since the early1900s.  The classical work of Walter Jacobs and Michael Heidelberger in 1915 put in perspective a then ongoing rather vitriolic debate about the structure of organomercuric compounds and conclusively proved beyond reasonable doubt the chemical structure of primary and secondary p-aminophenylmercury compounds.2
Due to raising concerns about human exposure to mercury compounds, several studies have focused on interaction of mercury with biological systems. Most of these interactions are supposedly mediated through the thiol groups on proteins.3 Thus rarely have interactions of mercury with groups other than those containing thiols in proteins and peptides ever been considered in the literature4
Several aromatic amines are orthomercurated and stabilized by weak N…. Hg interactions.5 Incorporation of these interactions in peptide side chains was the genesis of this study. We chose α,β – dehydroaminoacid residues as dehydrophenylalanine(ΔPhe) is found in bioactive peptides.6 Dehydrophenylalanine induces interesting biological and chemical properties. Peptides containing this residue show enhanced resistance to enzymatic degradation.7 They also enable a rich assortment of well-defined structural motifs, and are found in several naturally occurring compounds.7a,8 The achiral nature of ΔPhe residue allows it to be incorporated in both left and right handed helical conformations in peptides.9 The Z isomer is thermodynamically more stable and is indeed well studied.10 Studies of dehydropeptides have shown that these peptides are strong inducers of α-bends in short peptides and 310-helical conformations in long peptides.8,11 Occurrence of β-turns in conformationally restricted ΔPhe containing peptides and their characteristic i←i+3 intramolecular C=O…H-N bond in both solution and solid state has been reported by several groups.12 A notable number of ΔPhe containing peptides of varying length are reported to possess 310-helical conformation with both right- and left-handedness.12a,13 As Aib and ∆Z Phe are both achiral, the conformational energy calculations indicate that the preference of Aib containing peptides to form 310-helix overrides dehydrophenylalanine preferences in peptides containing both these residues.14  

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