New insights into coordination chemistry of Monensin A towards divalent metal ions

Pantcheva, Ivayla; Nedzhib, Ahmed; Antonov, Liudmil; Gyurcsik, Béla; Dorkov, Peter

doi:10.1016/j.ica.2020.119481

Cited by 5 publications

(9 citation statements)

References 36 publications

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“…A single isodichroic point around 240 nm, characteristic for the whole monitored c As III : c L 1 concentration ratio range, indicates that only one L 1 complex is in equilibrium with the free ligand. CD spectroscopic data on systems of “colorless” metal ions and ligands with chirality centers near the metal ion binding groups ,,,− indicate that the positive and negative CD bands with intensity extrema near 210 and 260 nm, respectively, can be assigned to the LMCT transitions (vide supra). The optical activity of L 1 is efficiently propagated from the α carbon chirality centers toward As III via the As III –thiolate bonds.…”

Section: Results and Discussionmentioning

confidence: 99%

Tristhiolato Pseudopeptides Bind Arsenic(III) in an AsS₃ Coordination Environment Imitating Metalloid Binding Sites in Proteins

et al. 2023

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The AsIII binding of two NTA-based tripodal pseudopeptides, possessing three cysteine (ligand L1 ) or d-penicillamine residues (ligand L2 ) as potential coordinating groups for soft semimetals or metal ions, was studied by experimental (UV, CD, NMR, and ESI-MS) and theoretical (DFT) methods. All of the experimental data, obtained with the variation of the AsIII:ligand concentration ratios or pH values in some instances, evidence the exclusive formation of species with an AsS3-type coordination mode. The UV-monitored titration of the ligands with arsenous acid at pH = 7.0 provided an absorbance data set that allowed for the determination of apparent stability constants of the forming species. The obtained stabilities (logK′ = 5.26 (AsL1 ) and logK′ = 3.04 (AsL2 )) reflect high affinities, especially for the sterically less restricted cysteine derivative. DFT calculated structures correlate well with the spectroscopic results and, in line with the 1H NMR data, indicate a preference for the all-endo conformers resembling the AsIII environment at the semimetal binding sites in various metalloproteins.

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Section: Results and Discussionmentioning

confidence: 99%

Tristhiolato Pseudopeptides Bind Arsenic(III) in an AsS₃ Coordination Environment Imitating Metalloid Binding Sites in Proteins

et al. 2023

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“…This fact simplifies the evaluation of the spectral series recorded during the titration experiments varying the molar ratio of the ligand and the metal ion. The stability of Ni(II) monensinates was found to be several orders of magnitude higher than that of other divalent metal complexes when evaluated with UV-CD spectroscopy [58]. This extremely high stability did not check up with the competitive properties of Ni(II) for monensinate.…”

Section: Resultsmentioning

confidence: 81%

“…Recent studies using synchrotron radiation circular dichroism spectroscopy in the ultraviolet wavelength range (UV-CD) have revealed that it can be successfully applied to evaluate the properties of monensinate complexes with M(I) and M(II) in methanolic solutions. The main advantages of the method consist in distinguishing the individual metal ions (especially the "colorless") thanks to the conformational changes (albeit in some cases very fine) in the monensinate structure occurring upon complexation [57,58]. Moreover, the solution chemistry of the antibiotic in the presence of di-and trivalent metal cations seems to be much more intricate, involving a number of equilibria in which diverse coordination species may exist in addition to the already observed and isolated ones.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the solution chemistry of the antibiotic in the presence of di-and trivalent metal cations seems to be much more intricate, involving a number of equilibria in which diverse coordination species may exist in addition to the already observed and isolated ones. Thus, at comparable or higher metal-to-ligand molar ratio, the ionophore is bound as [M(Mon)(H 2 O)] + (M = Mg(II), Ca(II), Mn(II), Co(II), Ni(II), Zn(II), Cd(II)) [58]. The close CD spectral features of neutral and charged species imply that the monensinate anion retains its coordination mode similarly to that observed in [M(Mon) 2 (H 2 O) 2 ].…”

Section: Introductionmentioning

confidence: 99%

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Circular Dichroism Spectroscopic Studies on Solution Chemistry of M(II)-Monensinates in Their Competition Reactions

et al. 2023

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The chirality of the polyether ionophore monensic acid A can be successfully used to study its coordination ability in solution. A complementary approach to gain new insights into the complexation chemistry of the antibiotic (studied previously by circular dichroism (CD) spectroscopy in the ultraviolet range (UV-CD)) is presented. (1) Methods: The CD spectroscopy in the visible (VIS-CD) and near-infrared (NIR-CD) range is applied to evaluate the affinity of deprotonated monensic acid A (monensinate A) towards Ni(II) or Co(II) cations in methanolic solution. Competition experiments between a variety of colorless divalent metal ions for binding the ligand anion were also performed. (2) Results: The stability constants of the species observed in binary Ni(II)/Co(II)-monensinate systems and their distribution were reevaluated with the VIS- and NIR-CD techniques. The data confirmed the formation of mono and bis complexes depending on the metal-to-ligand molar ratio. The studies on the systems containing two competing divalent metal cations exclude the formation of ternary complex species but provide an opportunity to also calculate the stability constants of Zn(II), Mg(II), and Ca(II) monensinates. (3) Conclusions: The advantages of CD spectroscopy in the VIS-NIR range (“invisible” ligand and metal salts, “visible” chiral complex species) simplify the experimental dataset evaluation and increase the reliability of computed results.

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“…Monensin and nigericin are also protonophores and act as H + shunts known to delay onset times of BoNT/A- and BoNT/B-treated muscles at low concentrations . Nigericin, a microbial toxin and a protonophore, permeabilizes K + and H + through the membrane, controlling the intracellular pH. , Monensin has been shown to form zwitterionic complexes with monovalent and divalent cations mechanizing as a transporter across the lipid membrane. ,− Niclosamide, a salicylanilide and an approved antihelminthic with antineoplastic and antiviral effects, exerts its effect by neutralizing endolysosomal pH . Unlike BafA1, it does not affect a protein target and is considered a proton carrier or a protonophore.…”

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confidence: 99%

Investigation of Salicylanilides as Botulinum Toxin Antagonists

et al. 2022

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Botulinum neurotoxin serotype A (BoNT/A) is recognized by the Centers for Disease Control and Prevention (CDC) as the most potent toxin and as a Tier 1 biowarfare agent. The severity and longevity of botulism stemming from BoNT/A is of significant therapeutic concern, and early administration of antitoxin–antibody therapy is the only approved pharmaceutical treatment for botulism. Small molecule therapeutic strategies have targeted both the heavy chain (HC) and the light chain (LC) catalytic active site and α-/β-exosites. The LC translocation mechanism has also been studied, but an effective, nontoxic inhibitor remains underexplored. In this work, we screened a library of salicylanilides as potential translocation inhibitors. Potential leads following a primary screen were further scrutinized to identify sal30, which has a cellular minimal concentration of a drug that is required for 50% inhibition (IC50) value of 141 nM. The inquiry of salicylanilide sal30’s mechanism of action was explored through a self-quenched fluorogenic substrate conjugated to bovine serum albumin (DQ-BSA) fluorescence, confocal microscopy, and vacuolar H+-ATPase (V-ATPase) inhibition assays. The summation of these findings imply that endolysosomal proton translocation through the protonophore mechanism of sal30 causes endosome pH to increase, which in turn prevents LC translocation into cytosol, a process that requires an acidic pH. Thus, the inhibition of BoNT/A activity by salicylanilides likely occurs through disruption of pH-dependent endosomal LC translocation. We further probed BoNT inhibition by sal30 using additivity analysis studies with bafilomycin A1, a known BoNT/A LC translocation inhibitor, which indicated the absence of synergy between the two ionophores.

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New insights into coordination chemistry of Monensin A towards divalent metal ions

Cited by 5 publications

References 36 publications

Tristhiolato Pseudopeptides Bind Arsenic(III) in an AsS₃ Coordination Environment Imitating Metalloid Binding Sites in Proteins

Tristhiolato Pseudopeptides Bind Arsenic(III) in an AsS₃ Coordination Environment Imitating Metalloid Binding Sites in Proteins

Circular Dichroism Spectroscopic Studies on Solution Chemistry of M(II)-Monensinates in Their Competition Reactions

Investigation of Salicylanilides as Botulinum Toxin Antagonists

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New insights into coordination chemistry of Monensin A towards divalent metal ions

Cited by 5 publications

References 36 publications

Tristhiolato Pseudopeptides Bind Arsenic(III) in an AsS3 Coordination Environment Imitating Metalloid Binding Sites in Proteins

Tristhiolato Pseudopeptides Bind Arsenic(III) in an AsS3 Coordination Environment Imitating Metalloid Binding Sites in Proteins

Circular Dichroism Spectroscopic Studies on Solution Chemistry of M(II)-Monensinates in Their Competition Reactions

Investigation of Salicylanilides as Botulinum Toxin Antagonists

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Product

Resources

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Tristhiolato Pseudopeptides Bind Arsenic(III) in an AsS₃ Coordination Environment Imitating Metalloid Binding Sites in Proteins

Tristhiolato Pseudopeptides Bind Arsenic(III) in an AsS₃ Coordination Environment Imitating Metalloid Binding Sites in Proteins