TNP

Small molecular probe as selective tritopic sensor of Al(3+), F(-) and TNP: Fabrication of portable prototype for onsite detection of explosive TNP.[Pubmed:28366208]

Anal Chim Acta. 2017 May 1;965:111-122.

Schiff base organic compound (SOC) has been prepared as a tritopic chemosensor for selective sensing by fluorescence signalling towards ions like Al(3+), F(-) and explosive molecule like TNP. In general, fluorescence like photophysical property has been used for selective detection of analyte where Al(3+) and F(-) show turn-on fluorescence signal at different wavelengths (nm) however, quenching was found with TNP. As a consequence, the chemosensor has become a selective sensor for Al(3+), F(-) and TNP. Reversibility of fluorescence responses for Al(3+) and F(-) are observed in presence of ammonium nitrate and H(+) respectively. Similar to the detection of TNP, the detection of explosive like NO3(-) salts is also essential from homeland security point of view. In the present work, the finding of reversible sequential fluorescence response can be promoted for fabrication of next generation AND-NOT-OR-NAND-XOR-XNOR-NOR based complex logic circuit which is applicable in photonics, security and other fields including inorganic and material science. In the case of TNP recognition, the pathway mainly depends on non-covalent interaction (quenching constant: 4.4 x 10(5) M(-1)) which is even better than the recently reported materials. Detection limit for Al(3+), F(-) and TNP is 1 muM, 3 muM and 500 nM respectively. DFT-D3 has been carried out to explore the hostcdots, three dots, centeredguest interaction along with the structure-property correlation of the present host-guest system. All three guest analytes have been detected inside the living cell at a certain level and in its consequence, the successful in vitro recognition ability of the SOCs inside human cell line HeLa has been explored too. In real time stepping, an easy to operate and an economically affordable pocket prototype has also been fabricated for on spot detection of TNP like explosive.

Multiple functional therapeutic effects of TnP: A small stable synthetic peptide derived from fish venom in a mouse model of multiple sclerosis.[Pubmed:28235052]

PLoS One. 2017 Feb 24;12(2):e0171796.

The pathological condition of multiple sclerosis (MS) relies on innate and adaptive immunity. New types of agents that beneficially modify the course of MS, stopping the progression and repairing the damage appear promising. Here, we studied TNP, a small stable synthetic peptide derived from fish venom in the control of inflammation and demyelination in experimental autoimmune encephalomyelitis as prophylactic treatment. TNP decreased the number of the perivascular infiltrates in spinal cord, and the activity of MMP-9 by F4/80+ macrophages were decreased after different regimen treatments. TNP reduces in the central nervous system the infiltration of IFN-gamma-producing Th1 and IL-17A-producing Th17 cells. Also, treatment with therapeutic TNP promotes the emergence of functional Treg in the central nervous system entirely dependent on IL-10. Therapeutic TNP treatment accelerates the remyelination process in a cuprizone model of demyelination. These findings support the beneficial effects of TNP and provides a new therapeutic opportunity for the treatment of MS.

A fluorescent probe based on nitrogen doped graphene quantum dots for turn off sensing of explosive and detrimental water pollutant, TNP in aqueous medium.[Pubmed:28262581]

Spectrochim Acta A Mol Biomol Spectrosc. 2017 Jun 5;180:37-43.

This paper reports the carbonization assisted green approach for the fabrication of nitrogen doped graphene quantum dots (N-GQDs). The obtained N-GQDs displayed good water dispersibility and stability in the wide pH range. The as synthesized N-GQDs were used as a fluorescent probe for the sensing of explosive 2,4,6-trinitrophenol (TNP) in aqueous medium based on fluorescence resonance energy transfer (FRET), molecular interactions and charge transfer mechanism. The quenching efficiency was found to be linear in proportion to the TNP concentration within the range of 0-16muM with detection limit (LOD) of 0.92muM. The presented method was successfully applied to the sensing of TNP in tap and lake water samples with satisfactory results. Thus, N-GQDs were used as a selective, sensitive and turn off fluorescent sensor for the detection of perilous water contaminant i.e. TNP.

Characterization of a selective inhibitor of inositol hexakisphosphate kinases: use in defining biological roles and metabolic relationships of inositol pyrophosphates.[Pubmed:19208622]

J Biol Chem. 2009 Apr 17;284(16):10571-82.

Inositol hexakisphosphate kinases (IP6Ks) phosphorylate inositol hexakisphosphate (InsP(6)) to yield 5-diphosphoinositol pentakisphosphate (5-[PP]-InsP(5) or InsP(7)). In this study, we report the characterization of a selective inhibitor, N(2)-(m-(trifluoromethy)lbenzyl) N(6)-(p-nitrobenzyl)purine (TNP), for these enzymes. TNP dose-dependently and selectively inhibited the activity of IP6K in vitro and inhibited InsP(7) and InsP(8) synthesis in vivo without affecting levels of other inositol phosphates. TNP did not inhibit either human or yeast Vip/PPIP5K, a newly described InsP(6)/InsP(7) 1/3-kinase. Overexpression of IP6K1, -2, or -3 in cells rescued TNP inhibition of InsP(7) synthesis. TNP had no effect on the activity of a large number of protein kinases, suggesting that it is selective for IP6Ks. TNP reversibly reduced InsP(7)/InsP(8) levels. TNP in combination with genetic studies was used to implicate the involvement of two pathways for synthesis of InsP(8) in yeast. TNP induced a fragmented vacuole phenotype in yeast, consistent with inhibition of Kcs1, a Saccharomyces cerevisiae IP6K. In addition, it also inhibited insulin release from Min6 cells in a dose-dependent manner further implicating InsP(7) in this process. TNP thus provides a means of selectively and rapidly modulating cellular InsP(7) levels, providing a new and versatile tool to study the biological function and metabolic relationships of inositol pyrophosphates.

TNP is a cell-permeable inhibitor of IP6K1 and IP3K, with IC50 values of 0.55 µM and 10.2 µM for IP3K, respectively. TNP binds to the ATP-binding sites of both enzymes.

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