NMR and molecular recognition. The application of ligand-based NMR methods to monitor molecular interactions

Unione, Luca; Galante, Silvia; Díaz, Dolores; Cañada, F. Javier; Jiménez‐Barbero, Jesús

doi:10.1039/c4md00138a

Cited by 45 publications

(28 citation statements)

References 96 publications

(107 reference statements)

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“…For this purpose, we employed both ligand-based and receptor-based NMR methods. [32] We have demonstrated, by using protein solubility assaysa nd FTIR spectroscopy,t hat the mechanismb yw hich both compounds,EGCG and tetracycline, affect JD aggregation is essentially the same as that observed in the case of expanded AT3. [13] These resultsf urtherd emonstrate the direct involvement of the JD in full-length AT3f ibrillation.…”

Section: Introductionmentioning

confidence: 75%

How Epigallocatechin‐3‐gallate and Tetracycline Interact with the Josephin Domain of Ataxin‐3 and Alter Its Aggregation Mode

Bonanomi

Visentin

Natalello

et al. 2015

Chemistry A European J

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Epigallocatechin-3-gallate (EGCG) and tetracycline are two known inhibitors of amyloid aggregation able to counteract the fibrillation of most of the proteins involved in neurodegenerative diseases. We have recently investigated their effect on ataxin-3 (AT3), the polyglutamine-containing protein responsible for spinocerebellar ataxia type 3. We previously showed that EGCG and tetracycline can contrast the aggregation process and toxicity of expanded AT3, although by different mechanisms. Here, we have performed further experiments by using the sole Josephin domain (JD) to further elucidate the mechanism of action of the two compounds. By protein solubility assays and FTIR spectroscopy we have first observed that EGCG and tetracycline affect the JD aggregation essentially in the same way displayed when acting on the full-length expanded AT3. Then, by saturation transfer difference (STD) NMR experiments, we have shown that EGCG binds both the monomeric and the oligomeric JD form, whereas tetracycline can only interact with the oligomeric one. Surface plasmon resonance (SPR) analysis has confirmed the capability of the sole EGCG to bind monomeric JD, although with a KD value suggestive for a non-specific interaction. Our investigations provide new details on the JD interaction with EGCG and tetracycline, which could explain the different mechanisms by which the two compounds reduce the toxicity of AT3.

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Section: Introductionmentioning

confidence: 75%

How Epigallocatechin‐3‐gallate and Tetracycline Interact with the Josephin Domain of Ataxin‐3 and Alter Its Aggregation Mode

Bonanomi

Visentin

Natalello

et al. 2015

Chemistry A European J

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“…[8] Particularly for large,p oorly solubleo rs carce target proteins the use of ligand-based NMR methods is indicated. [9] In this case, isotopes othert han 1 Hp resenti nt he ligand would be extremely helpful to allow itso bservation with highest specificity and spectral resolution. For instance, recent examples have highlighted the applicationo f 19 F [10] or 77 Se NMR [11] to detect molecular binding.…”

Section: Introductionmentioning

confidence: 99%

Monitoring Glycan–Protein Interactions by NMR Spectroscopic Analysis: A Simple Chemical Tag That Mimics Natural CH–π Interactions

Calle

Echeverría

Franconetti

et al. 2015

Chemistry A European J

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Detection of molecular recognition processes requires robust, specific, and easily implementable sensing methods, especially for screening applications. Here, we propose the difluoroacetamide moiety (an acetamide bioisoster) as a novel tag for detecting by NMR analysis those glycan-protein interactions that involve N-acetylated sugars. Although difluoroacetamide has been used previously as a substituent in medicinal chemistry, here we employ it as a specific sensor to monitor interactions between GlcNAc-containing glycans and a model lectin (wheat germ agglutinin). In contrast to the widely employed trifluoroacetamide group, the difluoroacetamide tag contains geminal (1) H and (19) F atoms that allow both (1) H and (19) F NMR methods for easy and robust detection of molecular recognition processes involving GlcNAc- (or GalNAc-) moieties over a range of binding affinities. The CHF2 CONH- moiety behaves in a manner that is very similar to that of the natural acetamide fragment in the involved aromatic-sugar interactions, providing analogous binding energy and conformations, whereas the perfluorinated CF3 CONH- analogue differs more significantly.

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“…1. The docking protocol can be validated using NMR would be an approach for the assessment of molecular recognition (Unione et al, 2014).…”

Section: Compoundmentioning

confidence: 99%

Molecular modelling, synthesis, and antimalarial potentials of curcumin analogues containing heterocyclic ring

Balaji

Ahsan²,

Jadav

et al. 2019

Arabian Journal of Chemistry

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The molecular modelling approach was applied to a series of nineteen curcumin analogues to find the possible PfRIO2 kinase inhibitory action. A putative active site in flexible loop (S1) of PfRIO2 kinase was explored computationally to recognize the molecular basis of ligands binding. The ligands (curcumin analogues; 3a-3s) were well accommodated in the selected active site (S1) due to their higher molecular size and length. Further all these synthesized compounds (3a-3s) were evaluated for their in vitro antimalarial activity according to the reported method. The antimalarial data showed that all these compounds to have parasiticidal activity with minimum killing concentrations (MKCs) range between 3.87 and 25.35 lM and schizonticidal activity with IC 50 range between 1.48 and 23.09 lM. The compound 3p showed the most significant result with maximum schizonticidal (IC 50 ; 1.48 ± 0.10 lM) and parasiticidal activities (MKC; 3.87 ± 0.36 lM) could be identified as promising lead for further investigations. ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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NMR and molecular recognition. The application of ligand-based NMR methods to monitor molecular interactions

Abstract: NMR allows the monitoring of molecular recognition processes in solution. Nowadays, a plethora of NMR methods are available to deduce the key features of the interaction from both the ligand or the receptor points of view.

Cited by 45 publications

References 96 publications

How Epigallocatechin‐3‐gallate and Tetracycline Interact with the Josephin Domain of Ataxin‐3 and Alter Its Aggregation Mode

How Epigallocatechin‐3‐gallate and Tetracycline Interact with the Josephin Domain of Ataxin‐3 and Alter Its Aggregation Mode

Monitoring Glycan–Protein Interactions by NMR Spectroscopic Analysis: A Simple Chemical Tag That Mimics Natural CH–π Interactions

Molecular modelling, synthesis, and antimalarial potentials of curcumin analogues containing heterocyclic ring

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