NMR and DFT studies of monounsaturated and ω-3 polyunsaturated free fatty acids in the liquid state reveal a novel atomistic structural model of DHA

Venianakis, Themistoklis; Siskos, Michael G.; Papamokos, George; Gerothanassis, Ioannis P.

doi:10.1016/j.molliq.2023.121459

Cited by 7 publications

(22 citation statements)

References 57 publications

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“…In recent work, the ability of DHA and EPA to adopt folded conformations was highlighted [45,46]. highlighted [45,46]. Our findings, corroborated by the scientific literature, suggest that FA3 may become a high-affinity pocket for long-chain polyunsaturated free fatty acids since their folded conformation matches the spatial arrangement demands of the site.…”

Section: The Binding Site Fa3supporting

confidence: 81%

“…The same anchoring sites with the standard distances of an electrostatic interaction were identified for EPA in poses two and seven, respectively. Our results also showed that DHA and EPA bound to HSA in FA7 via a folded structure, a common geometry for these FFAs in the liquid state [45,46]. Based on crystallographic ambiguity, FA7 was considered a lower affinity site for FFAs and a preferred spot for shorter FAs [23].…”

Section: Docking Calculations 221 the Binding Site Fa7mentioning

confidence: 56%

“…Binding affinity depends on the number of bis-allylic double bonds; both EPA and DHA possess a higher affinity with respect to caproleic, oleic, and linoleic acids, and it is only slightly weaker than that of warfarin (W) [27]. Polyunsaturated free fatty acids rapidly convert between a large number of conformers with structural motives such as spiral or hairpin motives in the liquid and solution states [45][46][47]. These pre-existing conformations, combined with the specific charge and hydrogen bond interactions, as well as π-interactions, of the polyunsaturated chains, may be the key properties for HSA-PUFA interactions in the FA7 binding site.…”

Section: Docking Calculations 221 the Binding Site Fa7mentioning

confidence: 99%

“…However, such U-bends may favor PUFAs since folding becomes an intrinsic property of FFAs with four and five bis-allylic double bonds. In recent work, the ability of DHA and EPA to adopt folded conformations was highlighted [45,46]. highlighted [45,46].…”

Section: The Binding Site Fa3mentioning

confidence: 99%

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Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations

et al. 2023

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Medium- and long-chain saturated and unsaturated free fatty acids (FFAs) are known to bind to human serum albumin (HSA), the main plasma carrier protein. Atomic-level structural data regarding the binding mode in Sudlow’s sites I (FA7) and II (FA4, FA3) of the polyunsaturated ω-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), however, are largely unknown. Herein, we report the combined use of saturation transfer difference (STD) and Interligand NOEs for Pharmacophore Mapping (INPHARMA) NMR techniques and molecular docking calculations to investigate the binding mode of DHA and EPA in Sudlow’s sites Ι and ΙΙ of HSA. The docking calculations and the significant number of interligand NOEs between DHA and EPA and the drugs warfarin and ibuprofen, which are stereotypical ligands for Sudlow’s sites I and II, respectively, were interpreted in terms of competitive binding modes and the presence of two orientations of DHA and EPA at the binding sites FA7 and FA4. The exceptional flexibility of the long-chain DHA and EPA and the formation of strongly folded structural motives are the key properties of HSA–PUFA complexes.

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Section: The Binding Site Fa3supporting

confidence: 81%

Section: Docking Calculations 221 the Binding Site Fa7mentioning

confidence: 56%

Section: Docking Calculations 221 the Binding Site Fa7mentioning

confidence: 99%

Section: The Binding Site Fa3mentioning

confidence: 99%

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Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations

et al. 2023

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“…The chemical shifts of the carboxylic protons, δ(COOH), and phenol OH group, δ(OH), are very informative criteria for the investigation of various types of hydrogen bond interactions [ 28 , 29 , 30 , 31 ]. δ(COOH) and δ(OH) are deshielded in the presence of hydrogen bond interactions, and linear correlations between 1 H NMR chemical shifts and hydrogen bond distances have been reported [ 30 , 31 ].…”

Section: Resultsmentioning

confidence: 99%

Structural Studies of Monounsaturated and ω-3 Polyunsaturated Free Fatty Acids in Solution with the Combined Use οf NMR and DFT Calculations—Comparison with the Liquid State

Venianakis,

Siskos,

Papamokos

et al. 2023

Molecules

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Molecular structures, in chloroform and DMSO solution, of the free fatty acids (FFAs) caproleic acid, oleic acid, α-linolenic acid, eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) are reported with the combined use of NMR and DFT calculations. Variable temperature and concentration chemical shifts of the COOH protons, transient 1D NOE experiments and DFT calculations demonstrate the major contribution of low molecular weight aggregates of dimerized fatty acids through intermolecular hydrogen bond interactions of the carboxylic groups, with parallel and antiparallel interdigitated structures even at the low concentration of 20 mM in CDCl3. For the dimeric DHA, a structural model of an intermolecular hydrogen bond through carboxylic groups and an intermolecular hydrogen bond between the carboxylic group of one molecule and the ω-3 double bond of a second molecule is shown to play a role. In DMSO-d6 solution, NMR and DFT studies show that the carboxylic groups form strong intermolecular hydrogen bond interactions with a single discrete solvation molecule of DMSO. These solvation species form parallel and antiparallel interdigitated structures of low molecular weight, as in chloroform solution. This structural motif, therefore, is an intrinsic property of the FFAs, which is not strongly affected by the length and degree of unsaturation of the chain and the hydrogen bond ability of the solvent.

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Visible-light excitable thermally activated delayed fluorescence from hydrogen-bonded D-A aromatic N-heterocycle/polymer material and the application for anti-counterfeiting

Zhang,

Zhou,

Yang

et al. 2024

Dyes and Pigments

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NMR and DFT studies of monounsaturated and ω-3 polyunsaturated free fatty acids in the liquid state reveal a novel atomistic structural model of DHA

Cited by 7 publications

References 57 publications

Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations

Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations

Structural Studies of Monounsaturated and ω-3 Polyunsaturated Free Fatty Acids in Solution with the Combined Use οf NMR and DFT Calculations—Comparison with the Liquid State

Visible-light excitable thermally activated delayed fluorescence from hydrogen-bonded D-A aromatic N-heterocycle/polymer material and the application for anti-counterfeiting

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