Primary Structure of Glycans by NMR Spectroscopy

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(3), P. 1040 - 1102

Published: Jan. 9, 2023

Glycans, carbohydrate molecules in the realm of biology, are present as biomedically important glycoconjugates and a characteristic aspect is that their structures many instances branched. In determining primary structure glycan, sugar components including absolute configuration ring form, anomeric configuration, linkage(s), sequence, substituents should be elucidated. Solution state NMR spectroscopy offers unique opportunity to resolve all these aspects at atomic resolution. During last two decades, advancement both experiments spectrometer hardware have made it possible unravel more efficiently. These developments applicable glycans include, inter alia, reduce spectral overlap, use selective excitations, record tilted projections multidimensional spectra, acquire spectra by multiple receivers, utilize polarization fast-pulsing techniques, concatenate pulse-sequence modules several single measurement, pure shift correlated devoid scalar couplings, employ stable isotope labeling efficiently obtain homo- and/or heteronuclear correlations, well those rely on dipolar cross-correlated interactions for sequential information. Refined computer programs spin simulation chemical prediction aid structural elucidation glycans, which notorious limited dispersion. Hardware include cryogenically cold probes dynamic nuclear resulting enhanced sensitivity ultrahigh field spectrometers with 1H resonance frequency higher than 1 GHz, thus improving resolution resonances. Taken together, will future make elucidate great detail, thereby forming basis understanding how interact other molecules.

Language: Английский

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Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs

Chemical Papers, Journal Year: 2023, Volume and Issue: 77(8), P. 4085 - 4106

Published: April 13, 2023

Language: Английский

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Advances in chemical probing of protein O-GlcNAc glycosylation: structural role and molecular mechanisms

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(18), P. 10451 - 10485

Published: Jan. 1, 2021

This review describes the recent developments in chemical probing of O -GlcNAcylation with a special focus on its molecular, structural and mechanistic implications.

Language: Английский

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Small, but powerful and attractive: 19F in biomolecular NMR

Structure, Journal Year: 2021, Volume and Issue: 30(1), P. 6 - 14

Published: Dec. 13, 2021

Language: Английский

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Fluorinated Rings: Conformation and Application

Chemistry - A European Journal, Journal Year: 2021, Volume and Issue: 27(25), P. 7193 - 7213

Published: Jan. 29, 2021

The introduction of fluorine atoms into molecules and materials across many fields academic industrial research is now commonplace, owing to their unique properties. A particularly interesting feature the impact substitution on relative orientation a C-F bond when incorporated organic molecules. In this Review, we will be discussing conformational behavior fluorinated aliphatic carbo- heterocyclic systems. preference each system associated with various interactions introduced by such as charge-dipole, dipole-dipole, hyperconjugative interactions. contribution interaction stabilization alicyclic system, which manifests itself in low conformations, discussed detail. novelty demonstrated presenting most recent applications.

Language: Английский

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Exploring multivalent carbohydrate–protein interactions by NMR

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(5), P. 1591 - 1613

Published: Jan. 1, 2023

Nuclear Magnetic Resonance (NMR) has been widely employed to assess diverse features of glycan–protein molecular recognition events.

Language: Английский

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Linkage-Editing Pseudo-Glycans: A Reductive α-Fluorovinyl-C-Glycosylation Strategy to Create Glycan Analogs with Altered Biological Activities

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(3), P. 2237 - 2247

Published: Jan. 10, 2024

The acetal (O-glycoside) bonds of glycans and glycoconjugates are chemically biologically vulnerable, therefore C-glycosides interest as more stable analogs. We hypothesized that, if the O-glycoside linkage plays a vital role in glycan function, biological activities C-glycoside analogs would vary depending on their substituents. Based this idea, we adopted "linkage-editing strategy" for creation (pseudo-glycans). designed three types pseudo-glycans with CH2 CHF linkages, which resemble terms bond lengths, angles, bulkiness, synthesized them efficiently by means fluorovinyl C-glycosylation selective hydrogenation reactions. Application strategy to isomaltose (IM), an inducer amylase expression, α-GalCer, activates iNKT cells, resulted discovery CH2-IM, shows increased production ability, CHF-α-GalCer, activity opposite that native serving antagonist cells.

Language: Английский

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The Role of Fluorine in Glycomimetic Drug Design

Chemistry - A European Journal, Journal Year: 2020, Volume and Issue: 27(7), P. 2240 - 2253

Published: Sept. 27, 2020

Abstract Glycans are well established to play important roles at various stages of infection and disease, ways modulate these interactions have been sought as novel therapies. The use native glycan structures has met with limited success, which can be attributed their characteristic high polarity (e.g., low binding affinities) inherently poor pharmacokinetic properties short drug–target residence times, rapid renal excretion), leading the development ′glycomimetics′. Fluorinated drugs become increasingly common over recent decades, fluorinated glycomimetics offering some unique advantages. Deoxyfluorination maintains certain electrostatic interactions, while concomitantly reducing net through ′polar hydrophobicity′, improving times affinities. Fluorination destabilizes oxocarbenium transition state associated metabolic degradation, restore exo ‐ endo ‐anomeric effects in C‐glycosides carbasugars. Lastly, it shown great utility radiotracer enhancement antigenicity glycan‐based vaccines. Owing synthetic challenges, somewhat underutilized date, but methodological improvements will advance glycomimetic drugs.

Language: Английский

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Sialidase Inhibitors with Different Mechanisms

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(20), P. 13574 - 13593

Published: Oct. 17, 2022

Sialidases, or neuraminidases, are enzymes that catalyze the hydrolysis of sialic acid (Sia)-containing molecules, mostly removal terminal Sia (desialylation). By desialylation, sialidase can modulate functionality target compound and is thus often involved in biological pathways. Inhibition sialidases with inhibitors an important approach for understanding function underlying mechanisms could serve as a therapeutic well. Transition-state analogues, such anti-influenza drugs oseltamivir zanamivir, major inhibitors. In addition, difluoro-sialic acids were developed mechanism-based Further, fluorinated quinone methide-based suicide substrates reported. Sialidase product analogue also explored. Finally, natural products have shown competitive inhibiton against viral, bacterial, human sialidases. This Perspective describes different their activities future potential, which include transition-state inhibitors, substrate

Language: Английский

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Modulating the Efficacy of Carbonic Anhydrase Inhibitors through Fluorine Substitution

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(43), P. 23068 - 23082

Published: May 24, 2021

The insertion of fluorine atoms and/or fluoroalkyl groups can lead to many beneficial effects in biologically active molecules, such as enhanced metabolic stability, bioavailability, lipophilicity, and membrane permeability, well a strengthening protein-ligand binding interactions. However, this "magic effect" atom(s) often be meaningless. Taking advantage the wide range data coming from quest for carbonic anhydrase (CA) fluorinated inhibitors, Minireview attempts give "general guidelines" on how wisely insert within an inhibitor moiety precisely enhance or disrupt ligand-protein interactions, depending target location substitution ligand. Multiple approaches ITC, kinetic inhibition studies, X-ray crystallography, NMR spectroscopy are useful dissecting single contributions overall observed effect. exploitation innovative directions made field protein ligand-based screening is also discussed avoid misconduct finely tune selective atom future.

Language: Английский

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