Membrane Transport Inspired Hydrolysis of Non-activated Esters at Near Physiological pH

Natural enzymes establish the proximity of the substrates to perform challenging reactions in aqueous medium, whereas most chemical catalysts typically follow stochastic way and are less efficient. Inspired by the membrane trafficking, a core biological process, herein we report that positively charged micro heterogeneous vehicles loaded with substrate could be trafficked suitably at the site of the reaction to promote the localization and proximity of the reactants. The guided vehicular delivery coupled with electrolysis overcomes the entropic barrier related to the proximity of the reactants and allows the hydrolysis of non-activated esters at physiological pH. Mechanistic investigations suggest that the reaction utilizes the electrochemical energy to generate hydroxide ion at the cathode and the positively charged micellar vehicles (loaded with substrates) trafficked selectively near cathode to promote the hydrolysis. The in situ modulation of surface charge was exploited to accelerate or inhibit the hydrolysis in a controlled manner akin to cofactors or zymogens of natural enzymes. We believe this elegant membrane trafficking inspired approach paves the way for the further applications of proximity controlled selective transformations in organic synthesis using green aqueous medium.<br>

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Membrane Trafficking Inspired Hydrolysis of Non-Activated Esters at Physiological pH

10.26434/chemrxiv.11919948.v1 ◽

2020 ◽

Author(s):

Pradip Kumar Tarafdar ◽

Suman De Sarkar ◽

Raki Mandal ◽

Kingshuk Mahanty ◽

Subhendu Mandal

Keyword(s):

Surface Charge ◽

Aqueous Medium ◽

Organic Synthesis ◽

Membrane Trafficking ◽

Biological Process ◽

Hydroxide Ion ◽

Activated Esters ◽

Hydrolysis Of ◽

Positively Charged

Natural enzymes establish the proximity of the substrates to perform challenging reactions in aqueous medium, whereas most chemical catalysts typically follow stochastic way and are less efficient. Inspired by the membrane trafficking, a core biological process, herein we report that positively charged micro heterogeneous vehicles loaded with substrate could be trafficked suitably at the site of the reaction to promote the localization and proximity of the reactants. The guided vehicular delivery coupled with electrolysis overcomes the entropic barrier related to the proximity of the reactants and allows the hydrolysis of non-activated esters at physiological pH. Mechanistic investigations suggest that the reaction utilizes the electrochemical energy to generate hydroxide ion at the cathode and the positively charged micellar vehicles (loaded with substrates) trafficked selectively near cathode to promote the hydrolysis. The in situ modulation of surface charge was exploited to accelerate or inhibit the hydrolysis in a controlled manner akin to cofactors or zymogens of natural enzymes. We believe this elegant membrane trafficking inspired approach paves the way for the further applications of proximity controlled selective transformations in organic synthesis using green aqueous medium.<br>

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Characteristics of the Interaction between Thrombin Exosite1 and the Sequence 269-297 of Platelet Glycoprotein Ibα

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615193 ◽

1998 ◽

Vol 80 (08) ◽

pp. 310-315 ◽

Cited By ~ 8

Author(s):

Marie-Christine Bouton ◽

Christophe Thurieau ◽

Marie-Claude Guillin ◽

Martine Jandrot-Perrus

Keyword(s):

Platelet Activation ◽

Electrostatic Interactions ◽

Platelet Glycoprotein ◽

Thrombin Receptor ◽

Central Position ◽

Amidolytic Activity ◽

N Terminus ◽

Hydrolysis Of ◽

Chemical Cross Linking ◽

Positively Charged

SummaryThe interaction between GPIb and thrombin promotes platelet activation elicited via the hydrolysis of the thrombin receptor and involves structures located on the segment 238-290 within the N-terminal domain of GPIbα and the positively charged exosite 1 on thrombin. We have investigated the ability of peptides derived from the 269-287 sequence of GPIbα to interact with thrombin. Three peptides were synthesized, including Ibα 269-287 and two scrambled peptides R1 and R2 which are comparable to Ibα 269-287 with regards to their content and distribution of anionic residues. However, R2 differs from both Ibα 269-287 and R1 by the shifting of one proline from a central position to the N-terminus. By chemical cross-linking, we observed the formation of a complex between 125I-Ibα 269-287 and α-thrombin that was inhibited by hirudin, the C-terminal peptide of hirudin, sodium pyrophosphate but not by heparin. The complex did not form when γ-thrombin was substituted for α-thrombin. Ibα 269-287 produced only slight changes in thrombin amidolytic activity and inhibited thrombin binding to fibrin. R1 and R2 also formed complexes with α-thrombin, modified slightly its catalytic activity and inhibited its binding to fibrin. Peptides Ibα 269-287 and R1 inhibited platelet aggregation and secretion induced by low thrombin concentrations whereas R2 was without effect. Our results indicate that Ibα 269-287 interacts with thrombin exosite 1 via mainly electrostatic interactions, which explains why the scrambled peptides also interact with exosite 1. Nevertheless, the lack of effect of R2 on thrombin-induced platelet activation suggests that proline 280 is important for thrombin interaction with GPIb.

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Synthesis of conjugates of 1-(carboxymethyl)cytosine and 1-(5-O-carboxymethyl-β-D-arabinofuranosyl)cytosine with proteins

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19793023 ◽

1979 ◽

Vol 44 (10) ◽

pp. 3023-3032 ◽

Cited By ~ 1

Author(s):

Helmut Pischel ◽

Antonín Holý ◽

Günther Wagner

Keyword(s):

Human Serum Albumin ◽

Acetic Anhydride ◽

Serum Albumin ◽

Human Serum ◽

Activated Esters ◽

Hydrolysis Of

1-(Carboxymethyl)cytosine (Ia), 1-(5-O-carboxymethyl-β-D-arabinofuranosyl)cytosine (IIa) and 5'-O-carboxylmethylcytidine (IIIa) were transformed by treatment with acetic anhydride and 4-dimethylaminopyridine to the peracetyl derivatives Ib-IIIb. These products reacted with p-nitrophenol in the presence of N, N'-dicyclohexylcarbodiimide to give the activated esters Ic-IIIc which on reaction with ammonia, dimethylamine or 2-aminoethanol afforded the corresponding carboxamides Id-IIId, IIe,f. Reactions of Ic and IIc with human serum albumin and bovine γ-globulin at pH 9.2, followed by hydrolysis of the N- or O-acetyl groups at pH 9.5, gave 50% up to 64% yields of the respective conjugates Ig, IIg and Ih, IIh.

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Structure of a Talaromyces pinophilus GH62 arabinofuranosidase in complex with AraDNJ at 1.25 Å resolution

Acta Crystallographica Section F Structural Biology Communications ◽

10.1107/s2053230x18000250 ◽

2018 ◽

Vol 74 (8) ◽

pp. 490-495 ◽

Cited By ~ 3

Author(s):

Olga V. Moroz ◽

Lukasz F. Sobala ◽

Elena Blagova ◽

Travis Coyle ◽

Wei Peng ◽

...

Keyword(s):

Plant Biomass ◽

Cellulosic Biomass ◽

Structural Basis ◽

Side Chain ◽

Polymeric Substrates ◽

Hydrolysis Of ◽

Insight Into ◽

Positively Charged ◽

Talaromyces Pinophilus ◽

Resolution Structure

The enzymatic hydrolysis of complex plant biomass is a major societal goal of the 21st century in order to deliver renewable energy from nonpetroleum and nonfood sources. One of the major problems in many industrial processes, including the production of second-generation biofuels from lignocellulose, is the presence of `hemicelluloses' such as xylans which block access to the cellulosic biomass. Xylans, with a polymeric β-1,4-xylose backbone, are frequently decorated with acetyl, glucuronyl and arabinofuranosyl `side-chain' substituents, all of which need to be removed for complete degradation of the xylan. As such, there is interest in side-chain-cleaving enzymes and their action on polymeric substrates. Here, the 1.25 Å resolution structure of the Talaromyces pinophilus arabinofuranosidase in complex with the inhibitor AraDNJ, which binds with a K d of 24 ± 0.4 µM, is reported. Positively charged iminosugars are generally considered to be potent inhibitors of retaining glycosidases by virtue of their ability to interact with both acid/base and nucleophilic carboxylates. Here, AraDNJ shows good inhibition of an inverting enzyme, allowing further insight into the structural basis for arabinoxylan recognition and degradation.

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Artificial Zinc Enzymes with Fine-Tuned Active Sites for Highly Selective Hydrolysis of Activated Esters

ACS Catalysis ◽

10.1021/acscatal.8b02292 ◽

2018 ◽

Vol 8 (9) ◽

pp. 8154-8161 ◽

Cited By ~ 15

Author(s):

MD Arifuzzaman ◽

Yan Zhao

Keyword(s):

Active Sites ◽

Selective Hydrolysis ◽

Activated Esters ◽

Zinc Enzymes ◽

Hydrolysis Of

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Conditions for the formation of bayerite and gibbsite

Mineralogical Magazine ◽

10.1180/minmag.1971.038.295.11 ◽

1971 ◽

Vol 38 (295) ◽

pp. 358-368 ◽

Cited By ~ 24

Author(s):

W. J. Mchardy ◽

A. P. Thomson

Keyword(s):

Electron Microscopy ◽

Carboxylic Acid ◽

Electron Diffraction ◽

Exchange Resin ◽

Anion Exchange Resin ◽

Acid Solutions ◽

Salt Solutions ◽

X Ray ◽

Hydrolysis Of ◽

Positively Charged

SummaryAluminium hydroxide gels have been prepared by the hydrolysis of amalgamated aluminium in water and by precipitation from aluminium salt solutions with an anion exchange resin in the hydroxyl form. The products crystallizing from such gels have been examined by electron microscopy and by X-ray and electron diffraction. Bayerite crystallizes as cone or pyramid-shaped particles and gibbsite as hexagonal plates or prisms. Two types of gel are postulated. The first type, pseudoboehmite, predominates in the absence of acids, is uncharged and rapidly crystallizes to bayerite; the second type, pregibbsite gel, occurs in carboxylic acid solutions, is positively charged and, in the absence of inorganic anions, crystallizes slowly to gibbsite.

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