- BIOMARKER PANEL TARGETED TO DISEASES DUE TO MULTIFACTORIAL ONTOLOGY OF GLYCOCALYX DISRUPTION
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The present disclosure provides biomarkers useful as companion diagnostics for detecting glycocalyx-based disease that is amenable to treatment using compounds designed for improving the condition of the glycocalyx and/or reducing inflammation and/or oxidative damage, as well as related compositions, kits, and methods.
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Paragraph 0304
(2021/04/02)
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- Lipase-catalyzed amidation of carboxylic acid and amines
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The amidation reaction is of a very particular interest, especially in the pharmaceutical industry and always requires the activation of the acid with a large excess of reactants. Therefore, a large amount of waste is generated. In order to reduce the environmental impact of such reaction, we have developed enzymatic amidation conditions which are compatible with a wide range of amines and acids, in particular with the biologically relevant lipoic acid. Water is the only by-product generated during this reaction thus a very high atom economy is obtained. In addition, we have shown that the lipase can be recovered and reused several times without a significant loss of activity.
- Manova, Daniela,Gallier, Florian,Tak-Tak, Lotfi,Yotava, Lyubov,Lubin-Germain, Nadège
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supporting information
p. 2086 - 2090
(2018/05/04)
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- Synthesis of a new family of protected 1,4,7,10-tetraazacyclododecane-1,4, 7-triacetic acid derivatives with thioctic acid pending arms
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The synthesis and characterization of a new family of ester protected N-substituted [1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (H3DO3A) derivatives containing a pendant thioctic acid (α lipoic acid, LA) are reported. These compounds (DO3AtBu-NLA, DO3AtBu-NMeNLA, and DO3AtBu-NEtNLA) are suitable for the functionalization of gold surfaces with rare-earth complexes.
- De La Reberdiere, Arnaud,Lachaud, Fabien,Chuburu, Francoise,Cadiou, Cyril,Lemercier, Gilles
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p. 6115 - 6118,4
(2020/08/20)
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- Redox cycling of β-lapachone and related o-naphthoquinones in the presence of dihydrolipoamide and oxygen
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Lipophilic o-naphthoquinones (β-lapachone, CG 8-935, CG 9-442, CG 10-248, and mansonones A, C, E, and F), catalyze the oxidation of dihydrolipoamide (DHLA) by oxygen, whereas p-naphthoquinones (α-lapachone and menadione) are scarcely active. The greatest effects corresponded to β-lapachone and its analogues. Quinol production was demonstrated by (a) the absorption spectrum of the reduced quinone, and (b) the effect of pH variation on the rate of quinone-catalyzed DHLA oxidation. Superoxide dismutase (SOD) inhibited the rate of cytochrome c reduction and decreased the apparent rate of oxygen consumption by several DHLA/o-naphthoquinone systems. SOD also inhibited the rate of quinol oxidation by oxygen, after quinone reduction by a stoichiometric amount of DHLA. Catalase enhanced the effect of SOD, but in its absence catalase was inactive. It is concluded that quinone-catalyzed oxidation of DHLA implies a free-radical mechanism in which the quinol and superoxide radicals play an essential role.
- Molina Portela, Maria P.,Stoppani, Andres O.M.
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p. 275 - 283
(2007/10/03)
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- Catalytic Oxidation of Dithiols by a Semisynthetic Enzyme
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The semisynthetic enzyme flavopapain (1C), obtained from the alkylation of Cys-25 of papain with 8α-(bromoacetyl)-10-methylisoalloxazine (1B), was found to be an effective catalyst for the oxidation of dithiols to disulfides.The k2/Ks values for the oxidation of d,l-dihydrolipoamide and d,l-dihydrolipoic acid determined from anaerobic single-reaction stopped-flow kinetics were 4400 and 3400 M-1 s-1, respectively.These values were, respectively, 126 and 200 times larger than the second-order rate constants for oxidation of d,l-dihydrolipoamide and d,l-dihydrolipoic acid by the model flavin 8-acetyl-10-methylisoalloxazine (1A).Under aerobic turnover conditions using the synthetic dye MTT as an electron acceptor, the kcat and Km values for the oxidation of d,l-dihydrolipoamide by 1C were in approximate agreement with the k2 and Ks values, indicating that the rate-limiting step of catalytic cycle is substrate oxidation rather than oxidation of dihydroflavopapain.When compared with flavopapains 2C and 3C , flavopapain 1C is the most efficient catalyst.The circular dichroic spectra of flavopapains 1C, 2C and 3C were recorded, and the dissociation constants of the sulfite addition complexes of 1C and 2C were determined.From these kinetic and physical studies, the differences in catalytic activity of 1C, 2C, and 3C were judged to be due to changes in the flavin orientation within the active site and the ability to fit the substrate into a productive reaction conformation.
- Stewart, Kent D.,Radziejewski, Czestaw,Kaiser, E. T.
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p. 3480 - 3483
(2007/10/02)
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- Oxidation of Dithiols by Flavopapain
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The redox reactions between flavopapain 1 and various dithiols have been examined under anaerobic conditions.The semisynthetic enzyme is an effective catalyst relative to the model flavin, 7-acetyl-10-methylisoalloxazine (3).Relative rate enhancements, (kcat/Km)/k2model, observed are 3.9, 8.0, and 17.4 for dithiotreitol, d,l-dihydrolipoic acid, and d,l-dihydrolipoamide, respectively.This substrate specificity, also seen in N-alkyl-1,4-dihydronicotinamide series, is explicable in terms of favorable hydrophobic-hydrophobic binding interaction between the substrates and the enzyme active site.Stereospecificity was not observed in the enzymatic reactions of the dithiols.It is demonstrated that the enzyme and model flavin reactions of the dithiols both proceeded via comparable mechanistic pathway.
- Fried, Herbert E.,Kaiser, E. T.
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p. 182 - 184
(2007/10/02)
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- Rate Constants and Equilibrium Constants for Thiol-Disulphide Interchange Reactions Involving Oxidized Glutathione
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The rate of reduction of oxidized glutathione (GSSG) to glutathione (GSH) by thiolate (RS-) follows a Broensted relation in pKas of the conjugate thiols (RSH): βnuc ca. 0.5.This value is similar to that for reduction of Ellman's reagent: βnuc ca. 0.4 - 0.5.Analysis of a number of rate and equilibrium data, taken both from this work and from the literature, indicates that rate constants, k, for a range of thiolate-disulphide interchange reactions are correlated well by equations of the form log k = C + βnucpKanuc + βcpKac + βlgpKalg ( nuc = nucleophile, c = central, and lg = leaving group sulfur): eq 36 - 38 give representative values of the Broensted coefficients.The values of these Bronsted coefficients are not sharply defined by the available experimental data, although eq 36 - 38 provide useful kinetic models for rates of thiolate-disulfide interchange reactions.The uncertainty in these parameters is such that their detailed mechanistic interpretation is not worthwhile, but their qualitative interpretation - that all three sulphur atoms experience a significant effective negative charge in the transition state, but that the charge is concentrated on the terminal sulfurs - is justified.Equilibrium constants for reduction of GSSG using α,ω-dithiols have been measured.The reducing potential of the dithiol is strongly influenced by the size of the cyclic disulfide formed on its oxidation: the most strongly reducing dithiols are those which can form six-membered cyclic disulfides.Separate equilibrium constants for thiolate anion-disulphide interchange (KS-) and for thiol-disufide interchange (KSH) have been estimated from literature data: KS- is roughly proportional to 2ΔpKa is the difference between the pKas of the two thiols involved in the interchange.The contributions of thiol pKa values to the observed equilibrium constants for reduction of GSSG with α,ω-dithiols appear to be much smaller than those ascribable to the influence of structure on intramolecular ring formation.These equilibrium and rate constants are helpful in choosing dithiols for use as antioxidants in solutions containing proteines: dithiothreitol (DTT), 1,3-dimercapto-2-propanol (DMP), and 2-mercaptoethanol have especially useful properties.
- Szajewski, Richard P.,Whitesides, George M.
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p. 2011 - 2026
(2007/10/02)
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