Rational Design of Benzyl-Type Protecting Groups Allows Sequential Deprotection of Hydroxyl Groups by Catalytic Hydrogenolysis

1998 ◽  
Vol 63 (13) ◽  
pp. 4172-4173 ◽  
Author(s):  
Matthew J. Gaunt ◽  
Jinquan Yu ◽  
Jonathan B. Spencer
Keyword(s):  
Rational Design ◽  
Protecting Groups ◽  
Hydroxyl Groups ◽  
Catalytic Hydrogenolysis

scholarly journals Efficient Refolding of Aggregation-prone Citrate Synthase by Polyol Osmolytes

2005 ◽  
Vol 280 (16) ◽  
pp. 15553-15560 ◽  
Author(s):  
Rajesh Mishra ◽  
Robert Seckler ◽  
Rajiv Bhat
Keyword(s):  
Small Molecules ◽  
Molecular Chaperones ◽  
Rational Design ◽  
Protein Production ◽  
Citrate Synthase ◽  
Protein A ◽  
Complete Recovery ◽  
Hydroxyl Groups ◽  
Native State

Efficient refolding of proteins and prevention of their aggregation during folding are of vital importance in recombinant protein production and in finding cures for several diseases. We have used citrate synthase (CS) as a model to understand the mechanism of aggregation during refolding and its prevention using several known structure-stabilizing cosolvent additives of the polyol series. Interestingly, no parallel correlation between the folding effect and the general stabilizing effect exerted by polyols was observed. Although increasing concentrations of polyols increased protein stability in general, the refolding yields for CS decreased at higher polyol concentrations, with erythritol reducing the folding yields at all concentrations tested. Among the various polyols used, glycerol was the most effective in enhancing the CS refolding yield, and a complete recovery of enzymatic activity was obtained at 7mglycerol and 10 μg/ml protein, a result superior to the action of the molecular chaperones GroEL and GroESin vitro. A good correlation between the refolding yields and the suppression of protein aggregation by glycerol was observed, with no aggregation detected at 7m. The polyols prevented the aggregation of CS depending on the number of hydroxyl groups in them. Stopped-flow fluorescence kinetics experiments suggested that polyols, including glycerol, act very early in the refolding process, as no fast and slow phases were detectable. The results conclusively demonstrate that both the thermodynamic and kinetic aspects are critical in the folding process and that all structure-stabilizing molecules need not always help in productive folding to the native state. These findings are important for the rational design of small molecules for efficient refolding of various aggregation-prone proteins of commercial and medical relevance.

Approaches to the preparation of 3'-deoxynucleosides

1968 ◽  
Vol 21 (2) ◽  
pp. 513 ◽  
Author(s):  
GAR Johnston
Keyword(s):  
Acyl Migration ◽  
Protecting Groups ◽  
Nucleophilic Displacement ◽  
Iodination Reaction ◽  
Catalytic Hydrogenolysis ◽  
The Stability ◽  
Derivatives Of

The stability of 3'-O-sulphonyl derivatives of uridine towards nucleophilic displacement indicates that sulphonate replacement is unlikely to offer a general route to 3'-deoxynucleosides. The preparation of 3'-deoxyuridine by direct iodination of 2',5'-di-O-trityluridine with triphenylphosphite methiodide followed by catalytic hydrogenolysis is discussed as such a general route dependent on the availability of suitably protected nucleoside starting materials. Acyl migration takes place under the conditions of the iodination reaction, limiting the choice of protecting groups.

scholarly journals Crystal structure of 6-azido-6-deoxy-1,2-O-isopropylidene-α-D-glucofuranose

2020 ◽  
Vol 76 (10) ◽  
pp. 1653-1656
Author(s):  
Adam Wood ◽  
Paul V. Bernhardt ◽  
Ian van Altena ◽  
Michela I. Simone
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bond ◽  
Biological Activities ◽  
Membered Ring ◽  
Protecting Groups ◽  
Hydroxyl Groups ◽  
Synthetic Strategy ◽  
Compound C ◽  
Hydrogen Bonding Interactions ◽  
Cross Links

Short syntheses to high Fsp 3 index natural-product analogues such as iminosugars are of paramount importance in the investigation of their biological activities and reducing the use of protecting groups is an advantageous synthetic strategy. An isopropylidene group was employed towards the synthesis of seven-membered ring iminosugars and the title compound, C9H15N3O5, was crystallized as an intermediate, in which the THF ring is twisted and the dioxolane ring adopts an envelope conformation: the dihedral angle between the rings is 67.50 (13)°. In the crystal, the hydroxyl groups participate in O—H...(O,O) and O—H...N hydrogen-bonding interactions, which generate chains of molecules propagating parallel to the a-axis direction. There is a notable non-classical C—H...O hydrogen bond, which cross-links the [100] chains into (001) sheets.

scholarly journals Achieving Macroscale Liquid Superlubricity Using Lubricant Mixtures of Glycerol and Diols

2021 ◽  
Author(s):  
Qiang Ma ◽  
Wei Wang ◽  
Guangneng Dong
Keyword(s):  
Rational Design ◽  
Friction And Wear ◽  
Surface Damage ◽  
Dynamics Simulation ◽  
Hydroxyl Groups ◽  
Ambient Atmosphere ◽  
Improve Energy Efficiency ◽  
Molecular Layers ◽  
Atmosphere Environment ◽  
Liquid Superlubricity

Abstract Friction and wear are ubiquitous in moving mechanical systems, and achieving vanishing friction and wear could significantly improve energy efficiency and extend the service life of mechanical components. In this paper, various diols, viz. ethylene glycol (EG), 1,3-propanediol (13-PD), and 1,2-propdiol (12-PD), have been selected to be mixed with glycerol for superlubricity performance. The results show that the lubricant mixture of EG and glycerol (EG/glycerol) and the mixture of 13-PD and glycerol (13-PD/glycerol) are effective in providing superlow friction (COF < 0.01) for steel tribopairs under ambient atmosphere environment with little surface damage caused. However, 12-PD, which exhibits the same chemical formula as 13-PD except for the configuration of hydroxyl groups, is ineffective for superlubrication. Furthermore, compared with 13-PD, EG is more efficient in preparing superlubric lubricants. Experimental and molecular dynamics simulation results show that the superlow friction realized by the lubricant mixtures of glycerol and diols is related to their intermolecular hydrogen-bonding interaction and the adsorbed formation of adsorbed molecular layers. The intermolecular interaction could affect the rheological property of lubricant mixtures and the hydrodynamic lubricant film-forming capability at the interface, while the quality of the adsorbed molecular layers determines the passivating efficiency for asperity interactions between opposite surfaces. Due to the atomic structure difference, EG is the most desirable diol for this objective, followed by 13-PD, while 12-PD is ineffective. These findings could help enable the rational design of novel lubricants for superlubricating performance and push the development of liquid superlubricity for future engineering applications.

Use of polymers as protecting groups in organic synthesis. III. Selective functionalization of polyhydroxy alcohols

1976 ◽  
Vol 54 (6) ◽  
pp. 926-934 ◽  
Author(s):  
Jean M. J. Fréchet ◽  
Lucy J. Nuyens
Keyword(s):  
Acidic Medium ◽  
Functional Group ◽  
Primary Alcohol ◽  
Protecting Groups ◽  
Hydroxyl Groups ◽  
Ether Linkage ◽  
Reaction Conditions ◽  
Selective Functionalization ◽  
One Step ◽  
Insoluble Polymers

Insoluble polymers containing trityl chloride residues were used to block one primary alcohol functional group of several polyhydroxy alcohols. After protecting the remaining hydroxyl groups by benzoylation, the ether linkage between the polymer and the protected alcohol was cleaved in acidic medium. Depending on the reaction conditions and the nature of the starting alcohol, several alcohols or bromides in which only one of the two primary hydroxyls had been esterified, were obtained. In some cases benzoyl migrations were observed. The trityl chloride polymers could be regenerated in one step without degradation or appreciable loss of activity.

scholarly journals Improving the Transglycosylation Activity of α-glucosidase From Xanthomonas Campestris Through Semi-rational Design for the Synthesis of Ethyl Vanillin-α-glucoside

2021 ◽  
Author(s):  
Luyi Chen ◽  
Yi Liu ◽  
Yaoyao Zhou ◽  
Linjiang Zhu ◽  
Xiaolong Chen
Keyword(s):  
Xanthomonas Campestris ◽  
Rational Design ◽  
Water Solubility ◽  
Catalytic Mechanism ◽  
Industrial Applications ◽  
Site Directed Mutagenesis ◽  
Aroma Compound ◽  
Hydroxyl Groups ◽  
Ethyl Vanillin ◽  
Transglycosylation Activity

Abstract The α-glucosidase (EC 3.2.1.20) Agl2 produced by Xanthomonas campestris shows high α-glucosyl transfer activity toward alcoholic and phenolic hydroxyl groups. Ethyl vanillin-α-glucoside, a precursor-aroma compound with improved water solubility and thermal stability, can be synthesized through the transglycosylation of ethyl vanillin by Agl2. However, its low ethyl vanillin-α-glucoside yield and ability to hydrolyze ethyl vanillin-α-glucoside limits for industrial applications. Rational design and site-directed mutagenesis were employed to generate three variants of X. campestris α-glucosidase: L145I, S272T and L145I/S272T, which displayed improved transglycosylation activity toward EV The ethyl vanillin-α-glucoside yield of L145I/S272T is the highest and is up to yield 52.41%. Besides, L145I/S272T also remarkably diminished the hydrolysis activity toward the transglycosylation product EVG compared to Agl2. Our rational design based the catalytic mechanism of the α-glucosidase reaction proved to be effective for producing mutants with improved the ratio of transglycosylation/hydrolysis of α-glucosidase, which provides an important theoretical basis for further research on the reaction mechanism of α-glucosidase.

scholarly journals Ligand-induced activation of human TRPM2 requires the terminal ribose of ADPR and involves Arg1433 and Tyr1349

2017 ◽  
Vol 474 (13) ◽  
pp. 2159-2175 ◽  
Author(s):  
Ralf Fliegert ◽  
Joanna M. Watt ◽  
Anja Schöbel ◽  
Monika D. Rozewitz ◽  
Christelle Moreau ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Rational Design ◽  
Transient Receptor Potential ◽  
Therapeutic Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Site Directed Mutagenesis ◽  
Structural Basis ◽  
Pharmacological Intervention ◽  
Hydroxyl Groups

TRPM2 (transient receptor potential channel, subfamily melastatin, member 2) is a Ca2+-permeable non-selective cation channel activated by the binding of adenosine 5′-diphosphoribose (ADPR) to its cytoplasmic NUDT9H domain (NUDT9 homology domain). Activation of TRPM2 by ADPR downstream of oxidative stress has been implicated in the pathogenesis of many human diseases, rendering TRPM2 an attractive novel target for pharmacological intervention. However, the structural basis underlying this activation is largely unknown. Since ADP (adenosine 5′-diphosphate) alone did not activate or antagonize the channel, we used a chemical biology approach employing synthetic analogues to focus on the role of the ADPR terminal ribose. All novel ADPR derivatives modified in the terminal ribose, including that with the seemingly minor change of methylating the anomeric-OH, abolished agonist activity at TRPM2. Antagonist activity improved as the terminal substituent increasingly resembled the natural ribose, indicating that gating by ADPR might require specific interactions between hydroxyl groups of the terminal ribose and the NUDT9H domain. By mutating amino acid residues of the NUDT9H domain, predicted by modelling and docking to interact with the terminal ribose, we demonstrate that abrogating hydrogen bonding of the amino acids Arg1433 and Tyr1349 interferes with activation of the channel by ADPR. Taken together, using the complementary experimental approaches of chemical modification of the ligand and site-directed mutagenesis of TRPM2, we demonstrate that channel activation critically depends on hydrogen bonding of Arg1433 and Tyr1349 with the terminal ribose. Our findings allow for a more rational design of novel TRPM2 antagonists that may ultimately lead to compounds of therapeutic potential.

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