Ultrasensitive electrochemical sensors based on Cu and Cu@Ag nanorods for simultaneous heavy metal detection

This work reports the development of ultrasensitive miniaturized electrochemical device for heavy metal sensing. A laser engraver based patterning of fluorine-doped tin oxide (FTO) sheet was done to draw an etched pattern forming a miniaturized 3-electrode configuration. A layer of Ag/AgCl ink served as pseudo-reference electrode. The sensing electrode was coated using low-cost Cu nanorods (CuNRs) grown radially along the {110} surface with aspect ratio of 8.0 and Cu@Ag core-shell nanorods (Cu@AgNRs) formed via galvanic displacement for simultaneous electrocatalytic detection of heavy metal ions (Pb(II), Cd(II), Hg(II), and Zn(II)) present in water. The electroactive surface area of the prepared devices is 0.026, 0.093 and 0.125 cm2 for bare FTO, CuNRs/FTO and Cu@AgNRs/FTO, respectively. Bimetal Cu@AgNRs/FTO sensor exhibited the lowest limit of detection of 1, 2, 5 and 6 nM, respectively, detecting Cd(II), Pb(II), Zn(II), and Hg(II) ions, and it was 2, 2, 3 and 4 nM, respectively, for simultaneous detection of Zn(II), Pb(II), Cd(II) and Hg(II). The Cu@AgNRs/FTO based device showed distinct peak-to-peak separation by 0.40, 0.25 and 0.51 V for Zn(II)-Cd(II), Cd(II)-Pb(II) and Pb(II)-Hg(II), respectively. This device was highly sensitive (583.6–1261.8 μA․μM−1․cm−2) for heavy metal detection over CuNRs/FTO (15.9–107.4 μA․μM−1․cm−2). The Cu@AgNRs/FTO based sensors demonstrated good reproducibility (relative standard deviation ≤ 5%) with recovery (>90%) in the case of all target heavy metals simultaneously present in environmental water samples. Hence, the Cu nanorods based miniaturized sensing platforms developed in the present study for simultaneous heavy metal detection are potential low-cost alternatives providing a repeatability of upto 4 cycles unlike the commercial screen-printed electrodes

A Novel Enediynyl Peptide Inhibitor of Furin That Blocks Processing of proPDGF-A, B and proVEGF-C

BACKGROUND: Furin represents a crucial member of secretory mammalian subtilase, the Proprotein Convertase (PC) or Proprotein Convertase Subtilisin/Kexin (PCSK) superfamily. It has been linked to cancer, tumorgenesis, viral and bacterial pathogenesis. As a result it is considered a major target for intervention of these diseases. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we report, for the first time, the synthesis and biological evaluation of a newly designed potent furin inhibitor that contains a highly reactive beta-turn inducing and radical generating "enediynyl amino acid" (Eda) moiety. "Eda" was inserted between P1 and P1' residues of hfurin(98-112) peptide, derived from the primary cleavage site of furin's own prodomain. The resulting hexadecapeptide derivative inhibited furin in vitro with IC(50) approximately 40 nM when measured against the fluorogenic substrate Boc-RVRR-MCA. It also inhibited furin-mediated cleavage of a fluorogenic peptide derived from hSARS-CoV spike protein with IC(50) approximately 193 nM. Additionally it also blocked furin-processing of growth factors proPDGF-A, B and VEGF-C that are linked to tumor genesis and cancer. Circular dichroism study showed that this inhibitor displayed a predominantly beta-turn structure while western blots confirmed its ability to protect furin protein from self degradation. CONCLUSION/SIGNIFICANCE: These findings imply its potential as a therapeutic agent for intervention of cancer and other furin-associated diseases

Design and synthesis of a novel enediynyl pentapeptide with predominantly β-turn structural motif and its potential as a fluorescence-based chemosensor

A novel enediynyl pentapeptide in the protected form 1 was synthesized and characterized. It exists predominantly in β-turn structural motif as revealed by variable temperature NMR and CD spectroscopy. In the presence of transition metal ions and gold nanoparticles, the fluorescence intensity of the peptide got enhanced with remarkable quantum yield with the Z-enediynyl -amino acid acting as a fluorophoric reporter. The interesting photophysical behaviors with alkali and alkaline earth metal ions are also reported

Isothiocyanyl Alanine as a Synthetic Intermediate for the Synthesis of Thioureayl Alanines and Subsequent Aminotetrazolyl Alanines

The synthesis of unnatural amino acids with small side-chain functionalities usable for further transformations is highly demanding for the expansion of the genetic code and other possible biotechnological applications. To this end, we wanted to report the utility of an unexplored unnatural amino acid, isothiocyanyl alanine (^NCSAla = Ita), for the synthesis of another class of unnatural amino acids, thioureayl alanines (^TUAla = Tua). The synthesis of a third class of unnatural amino acids, amino tetrazolyl alanines (^ATzAla = Ata), in a very good yield was subsequently achieved utilizing thioureayl alanines. Thus, a variety of aliphatic- and aromatic-substituted thioureayl alanines and aromatic-substituted amino tetrazolyl alanines were successfully synthesized in good to excellent yields. The photophysical properties of three of the fluorescent unnatural amino acids from two classes were also studied and presented herein

Design of “Click” Fluorescent Labeled 2′-deoxyuridines via C5-[4-(2-Propynyl(methyl)amino)]phenyl Acetylene as a Universal Linker: Synthesis, Photophysical Properties, and Interaction with BSA

Microenvironment-sensitive fluorescent nucleosides present attractive advantages over single-emitting dyes for sensing inter-biomolecular interactions involving DNA. Herein, we report the rational design and synthesis of triazolyl push–pull fluorophore-labeled uridines via the intermediacy of C5-[4-(2-propynyl­(methyl)­amino)]­phenyl acetylene as a universal linker. The synthesized nucleosides showed interesting solvatochromic characteristic and/or intramolecular charge transfer (ICT) features. A few of them also exhibited dual-emitting characteristics evidencing our designing concept. The HOMO–LUMO distribution showed that the emissive states of these nucleosides were characterized with more significant electron redistribution between the C5-[4-(2-propynyl­(methyl)­amino)]­phenyl triazolyl donor moiety and the aromatic chromophores linked to it, leading to modulated emission property. The solvent polarity sensitivity of these nucleosides was also tested. The synthesized triazolyl benzonitrile (<b>10C</b>), naphthyl (<b>10E</b>), and pyrenyl (<b>10G</b>) nucleosides were found to exhibit interesting ICT and dual (LE/ICT) emission properties. The dual-emitting pyrenyl nucleoside maintained a good ratiometric response in the BSA protein microenvironment, enabling the switch-on ratiometric sensing of BSA as the only protein biomolecule. Thus, it is expected that the new fluorescent nucleoside analogues would be useful in designing DNA probes for nucleic acid analysis or studying DNA–protein interactions via a drastic change in fluorescence response due to a change in micropolarity