- Reactivity Control in Micelles and Surfactant Vesicles. Kinetics and Mechanism of Base-Catalyzed Hydrolysis of 5,5'-Dithiobis(2-nitrobenzoic acid) in Water, Hexadecyltrimethylammonium Bromide Micelles, and Dioctadecyldimethylammonium Chloride Surfactant V
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Rate constants have been determined for the hydrolysis of 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) as functions of hydroxide ion concentrations in water, micellar hexadecyltrimethylammonium bromide (CTAB), and dioctadecyldimethylammonium chloride (DODAC
- Fendler, Janos H.,Hinze, Willie L.
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Read Online
- The Role of a Nonribosomal Peptide Synthetase in l -Lysine Lactamization during Capuramycin Biosynthesis
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Capuramycins are one of several known classes of natural products that contain an l-Lys-derived l-α-amino-caprolactam (l-ACL) unit. The α-amino group of l-ACL in a capuramycin is linked to an unsaturated hexuronic acid component through an amide bond that was previously shown to originate by an ATP-independent enzymatic route. With the aid of a combined in vivo and in vitro approach, a predicted tridomain nonribosomal peptide synthetase CapU is functionally characterized here as the ATP-dependent amide-bond-forming catalyst responsible for the biosynthesis of the remaining amide bond present in l-ACL. The results are consistent with the adenylation domain of CapU as the essential catalytic component for l-Lys activation and thioesterification of the adjacent thiolation domain. However, in contrast to expectations, lactamization does not require any additional domains or proteins and is likely a nonenzymatic event. The results set the stage for examining whether a similar NRPS-mediated mechanism is employed in the biosynthesis of other l-ACL-containing natural products and, just as intriguingly, how spontaneous lactamization is avoided in the numerous NRPS-derived peptides that contain an unmodified l-Lys residue.
- Liu, Xiaodong,Jin, Yuanyuan,Cui, Zheng,Nonaka, Koichi,Baba, Satoshi,Funabashi, Masanori,Yang, Zhaoyong,Van Lanen, Steven G.
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Read Online
- Synthesis and investigation of inhibitory activities of imidazole derivatives against the metallo-β-lactamase IMP-1
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Mutations in bacteria can result in antibiotic resistance due to the overuse or abuse of β-lactam antibiotics. One strategy which bacteria can become resistance toward antibiotics is secreting of metallo β-lactamase enzymes that can open the lactam ring of the β-lactam antibiotic and inactivate them. This issue is a threat for human health and one strategy to overcome this situation is co-administration of β-lactam antibiotics with an inhibitor. So far, no clinically available inhibitors of metallo β-lactamases (MBLs) reported and the clinically inhibitors of serine β-lactamase are useless for MBLs. Accordingly, finding a potent inhibitor of the MBLs being very important. In this study, imidazole derivatives primarily were synthesized and their inhibitory activity were measured. Later in silico binding model was used to predict the configuration and conformation of the ligands into the active site of enzyme. Two molecules demonstrated with IC50 of 39 μM and 46 μM against MBL (IMP-1).
- Khalili Arjomandi, Omid,Kavoosi, Mahboubeh,Adibi, Hadi
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- Tandem driven dynamic self-inhibition of acetylcholinesterase
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A concept of tandem driven dynamic self-inhibition is demonstrated through dynamic inhibitors of acetylcholinesterase (AChE) using reversible transthiolesterification.
- Zhang, Yan,Angelin, Marcus,Larsson, Rikard,Albers, Antonia,Simons, Adrian,Ramstroem, Olof
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supporting information; experimental part
p. 8457 - 8459
(2010/12/29)
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- Biological catalysis regulated by cucurbit[7]uril molecular containers
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We report the synthesis of two-faced inhibitors 1-5 that contain both enzyme inhibitor and cucurbit[n]uril binding domains. The enzyme binding domains of 1 -5 bind to the active sites of bovine carbonic anhydrase (BCA) or acetylcholinesterase (AChE) and inhibit their catalytic activities. Addition of CB[7] to BCA·1 and BCA·2 results In the transient formation of the BCA·1·CB[7] and BCA·2·CB[7] ternary complexes that undergo rapid dissociation to form free catalytically active BCA along with CB[7]·1 and CB[7]·2. The on-off cycle can be performed repetitively by the sequential addition of competitive guest 8 and CB[7], The detailed origins of this on-off switching of the catalytic activity of BCA is delineated by the combined inference of UV/vis catalytic assays, fluorescence displacement assays, 1H NMR, along with measurement of the fundamental values of Ka, Kon, and Koff for the various complexes involved. In contrast, addition of CB[7] to AChE·44 and AChE·54 results In the formation of thermodynamically stable ternary complexes AChE·44· CB[7]4 and AChE·54·;CB[7]4 that are catalytically inactive. We highlight some of the advantages and disadvantages of the strategy, based on the direct competition between two receptors (e.g., enzyme and CB[7]) for a common inhibitor, used In this paper to control enzyme catalytic activity compared to the strategy employed by Nature involving the binding of an allosteric small molecule remote from the enzyme active site.
- Ghosh, Soumyadip,Isaacs, Lyle
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scheme or table
p. 4445 - 4454
(2010/06/13)
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- THIONO COMPOUNDS. 10. STRUCTURES AND REACTIONS OF INTERMEDIAATES FROM THE OXIDATION OF PHOSPHOROTHIOATES
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Intermediates from the oxidation of phosphorothioates, (RO)3PS, were studied previously at low temperature using 31P NMR, UV and Raman spectra.Now reported is further information about the structure of intermediates and about their reactions, both of which afford significant clues as to how phosphorothioates may produce adverse biological reactions after they have ben oxidized biologically.Mass spectra identified intermediates corresponding to (RO)3PSn with n up to 7 (although presence of some equivalent masses with two oxygens in place of a sulfur atom is possible).HPLC separated unstable intermediates for which UV and MS evidence again was consistent with the structure (RO)3PSn.That intermediates can react as nucleophiles is illustrated by reactions with Ellman's Reagent, which produced a maximum of thiolate ion at about the time 31P NMR and UV indicated a maximum of intermediates.A second illustration of nucleophilicity was reaction with N-ethylmaleimide (and other Michael acceptors), which led to thiiranes and thiirane 1-oxides.That the intermediates can react also as electrophiles is illustrated by reactions (followed by UV and 31P NMR) with trimethyl phosphite, hydroxyl ion, and water (perhaps to some extent); use of H2(18)O did not introduce (18)O into phosphate products, but exchange reactions with H2(18)O did indicate presence of oxygenated species among the intermadiates.Keywords: Ellman's Reagent; N-ethylmaleimide; 31P NMR spectra; Phosphorothioates; Thiiranes; UV spectra.
- Swinson, Joel,Field, Lamar,Heimer, Norman E.,Stone, Michael P.,Wazer, John R. Van
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- Transvesicular Reactions of Thiols with Ellman's Reagent
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The cleavage of Ellman's reagent , 1, to chromophoric anion 2 by various thiols has been studied in pH 8 buffer, micellar cetyltrimethylammonium bromide (4), and vesicular dihexa-decyldimethylammonium bromide (5) or dioctadecyldimethylammonium chloride (6) solutions.The thiols included thiocholesterol, thiophenol, 2-thionaphthol, DL-cysteine, glutathione, 1-butanethiol, and 1-octanethiol.Vesicles of 6 at 25 deg C sequester 1 in distinct exovesicular and endovesicular binding sites, where reactions with added thiols are kinetically differentiated.Differences in thiol acidity and structure influence their rates of permeation and reaction with vesicle-bound 1.Small quantities of covesicallized 1-hexanol (0.2 wt percent) lower the gel to liquid crystalline transition temperature of vesicular 1 (from ca. 39 deg C to 24 deg C), enhance vesicular fluidity, accelerate the thiol/1 reactions, and destroy the kinetic distinction between the exovesicular and endovesicular reactions.
- Moss, Robert A.,Swarup, Shanti
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p. 5860 - 5866
(2007/10/02)
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- CLEAVAGE OF DISULFIDE DEPENDENT ON SUPEROXIDE
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Disulfide bond was cleaved by superoxide in aprotic media and by a hydroxyl radical derived from superoxide in aqueous medium.The reaction mechanism was examined in detail.
- Inoue, Hideshi,Nagano, Tetsuo,Hirobe, Masaaki
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p. 317 - 320
(2007/10/02)
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- Effect of Solvation on the Nucleophilic Reaction of Stable Carbanions with Diaryl Disulfides
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Stable carbanions react with diaryl disulfides in aqueous solution by direct displacement (SN2) reaction to yield an arylthiol anion and the corresponding sulfide as products.The reaction of 1,3-dicarbonyl carbanions with 5,5'-dithiobis(2-nitrobenzoic acid) is characterized by Broensted βC value of 0.5.Nitroalkane carbanions react 102-104 slower than 1,3-dicarbonyl carbanions of the same pK and are correlated by a Broensted βC of 0.95.The second-order rate constants for the reaction of nitroalkane carbanions increase by factors of 104-106 as the solvent is changed from water to dimethyl sulfoxide.Smaller increases are observed in the rate constants for reaction of 2,4-pentadienone carbanion (102) and malonitrile carbanion (100.6) with the same sulfide.A linear correlation is found between log (kMe2SO4/kHOH) and the increase in pK for the carbon acid ionization on changing the solvent from water to dimethyl sulfoxide.The effect is attributed to large differences in ground-state carbanion solvation which are reduced or absent in the transition state.Parallels are drawn between the nucleophilic reaction of stable carbanions with diaryl disulfides and proton-transfer reactions of the same carbanions.
- Gilbert, H. F.
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p. 7059 - 7065
(2007/10/02)
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