Zinc Photocages with Improved Photophysical Properties and Cell Permeability Imparted by Ternary Complex Formation

2019 ◽  
Vol 141 (30) ◽  
pp. 12100-12108 ◽  
Author(s):  
Prem N. Basa ◽  
Chelsea A. Barr ◽  
Kady M. Oakley ◽  
Xiaomeng Liang ◽  
Shawn C. Burdette
Keyword(s):  
Complex Formation ◽  
Ternary Complex ◽  
Photophysical Properties ◽  
Cell Permeability ◽  
Ternary Complex Formation

Zinc Photocages with Improved Photophysical Properties and Cell Permeability Imparted by Ternary Complex Formation

2019 ◽  
Author(s):  
Prem N. Basa ◽  
Chelsea A Barr ◽  
Kady M Oakley ◽  
Xiaomeng Liang ◽  
Shawn Burdette
Keyword(s):  
Acetic Acid ◽  
Ternary Complex ◽  
Photophysical Properties ◽  
Bidentate Ligand ◽  
Fluorescent Imaging ◽  
Cell Permeability ◽  
Rt Pcr ◽  
Cellular Processes ◽  
Ternary Complex Formation

Photocaged complexes have demonstrated efficacy as tools to control the availability of bioactive metals in cells to interrogate signaling pathways. We describe the synthesis of two new photocages, {bis[(2-pyridyl)methyl]amino}(9-oxo-2-xanthenyl)acetic acid (XDPAdeCage, <b>1</b>) {bis[(2-pyridyl)methyl]amino}(m-nitrophenyl)acetic acid (DPAdeCage, <b>2</b>), which utilize a 4-xanthone acetic acid and <i>meta</i>-nitrobenzyl chromophore respectively, to mediate a photodecarboxylation reaction. Both photocages strongly coordinate Zn<sup>2+</sup> and the binding equilibrium shifts significantly toward free Zn<sup>2+</sup> upon the decarboxylation of the chelator. XDPAdeCage photolyzes with quantum yield of 27% with 365 nm light, and binds Zn<sup>2+</sup> with 4.6 pM affinity, which decreases by over 4 orders of magnitude upon uncaging. A neutral form of [Zn(XDPAdeCage)]<sup>+</sup> can be generated <i>in situ</i> using the anionic bidentate ligand pyrithione, which imparts membrane impermeability to the ternary complex. Using fluorescent imaging, we have confirmed transport of Zn<sup>2+</sup> across lipophilic membranes; in addition, RT-PCR experiments demonstrate the photocaged complexes ability to perturb cellular processes after photolysis by showing a change in the expression levels of metallothionein and zinc transporter proteins.

Zinc Photocages with Improved Photophysical Properties and Cell Permeability Imparted by Ternary Complex Formation

2019 ◽  
Author(s):  
Prem N. Basa ◽  
Chelsea A Barr ◽  
Kady M Oakley ◽  
Xiaomeng Liang ◽  
Shawn Burdette
Keyword(s):  
Acetic Acid ◽  
Ternary Complex ◽  
Photophysical Properties ◽  
Bidentate Ligand ◽  
Fluorescent Imaging ◽  
Cell Permeability ◽  
Rt Pcr ◽  
Cellular Processes ◽  
Ternary Complex Formation

Photocaged complexes have demonstrated efficacy as tools to control the availability of bioactive metals in cells to interrogate signaling pathways. We describe the synthesis of two new photocages, {bis[(2-pyridyl)methyl]amino}(9-oxo-2-xanthenyl)acetic acid (XDPAdeCage, <b>1</b>) {bis[(2-pyridyl)methyl]amino}(m-nitrophenyl)acetic acid (DPAdeCage, <b>2</b>), which utilize a 4-xanthone acetic acid and <i>meta</i>-nitrobenzyl chromophore respectively, to mediate a photodecarboxylation reaction. Both photocages strongly coordinate Zn<sup>2+</sup> and the binding equilibrium shifts significantly toward free Zn<sup>2+</sup> upon the decarboxylation of the chelator. XDPAdeCage photolyzes with quantum yield of 27% with 365 nm light, and binds Zn<sup>2+</sup> with 4.6 pM affinity, which decreases by over 4 orders of magnitude upon uncaging. A neutral form of [Zn(XDPAdeCage)]<sup>+</sup> can be generated <i>in situ</i> using the anionic bidentate ligand pyrithione, which imparts membrane impermeability to the ternary complex. Using fluorescent imaging, we have confirmed transport of Zn<sup>2+</sup> across lipophilic membranes; in addition, RT-PCR experiments demonstrate the photocaged complexes ability to perturb cellular processes after photolysis by showing a change in the expression levels of metallothionein and zinc transporter proteins.

scholarly journals The acute transcriptional responses to dietary methionine restriction are triggered by inhibition of ternary complex formation and linked to Erk1/2, mTOR, and ATF4

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kirsten P. Stone ◽  
Sujoy Ghosh ◽  
Jean Paul Kovalik ◽  
Manda Orgeron ◽  
Desiree Wanders ◽  
...  
Keyword(s):  
Stress Response ◽  
Complex Formation ◽  
Ternary Complex ◽  
Target Genes ◽  
Bioinformatic Analysis ◽  
Transcriptional Responses ◽  
Metabolomics Data ◽  
Ternary Complex Formation ◽  
Methionine Restriction

AbstractThe initial sensing of dietary methionine restriction (MR) occurs in the liver where it activates an integrated stress response (ISR) that quickly reduces methionine utilization. The ISR program is regulated in part by ATF4, but ATF4’s prototypical upstream regulator, eIF2α, is not acutely activated by MR. Bioinformatic analysis of RNAseq and metabolomics data from liver samples harvested 3 h and 6 h after initiating MR shows that general translation is inhibited at the level of ternary complex formation by an acute 50% reduction of hepatic methionine that limits formation of initiator methionine tRNA. The resulting ISR is induced by selective expression of ATF4 target genes that mediate adaptation to reduced methionine intake and return hepatic methionine to control levels within 4 days of starting the diet. Complementary in vitro experiments in HepG2 cells after knockdown of ATF4, or inhibition of mTOR or Erk1/2 support the conclusion that the early induction of genes by MR is partially dependent on ATF4 and regulated by both mTOR and Erk1/2. Taken together, these data show that initiation of dietary MR induces an mTOR- and Erk1/2-dependent stress response that is linked to ATF4 by the sharp, initial drop in hepatic methionine and resulting repression of translation pre-initiation.

Ternary complex formation of the nickel(II), 2,2’-bipyridine, 1,10’-Phenanthroline and some aminoacids

2021 ◽  
pp. 1-11
Author(s):  
Yoselin Jara ◽  
Mary Lorena Araujo ◽  
Waleska Madden ◽  
Vito Lubes ◽  
Lino Hernández
Keyword(s):  
Complex Formation ◽  
Ternary Complex ◽  
Ternary Complex Formation

VPS37 Isoforms Differentially Modulate the Ternary Complex Formation of ALIX, ALG-2, and ESCRT-I

2013 ◽  
Vol 77 (8) ◽  
pp. 1715-1721 ◽  
Author(s):  
Mayumi OKUMURA ◽  
Angela M. KATSUYAMA ◽  
Hideki SHIBATA ◽  
Masatoshi MAKI
Keyword(s):  
Complex Formation ◽  
Ternary Complex ◽  
Ternary Complex Formation
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