N+-C-H···O Hydrogen bonds in protein-ligand complexes

Itoh, Yukihiro; Nakashima, Yusuke; Tsukamoto, Shuichiro; Kurohara, Takashi; Suzuki, Miki; Sakae, Yoshitake; Oda, Masayuki; Okamoto, Yuko; Suzuki, Takayoshi

doi:10.1038/s41598-018-36987-9

Cited by 118 publications

(83 citation statements)

References 38 publications

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“…The task of the present study was to elucidate if the physiological polymer polyP can bind to the surface of the SARS-CoV-2 S-protein via electrostatic linkages. The geometry and the spacing between two aa within the peptide perfectly fit with the length of 2.0 to 2.5 Å [55] . These distances match noticeably well with the length in the polyP chain between two phosphate anhydride linkages of 2.7 Å [17] .…”

Section: Discussionmentioning

confidence: 77%

The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations

Neufurth

Wang

Tolba

et al. 2020

Biochemical Pharmacology

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Section: Discussionmentioning

confidence: 77%

The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations

Neufurth

Wang

Tolba

et al. 2020

Biochemical Pharmacology

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“…The prevalence of C–H⋯O interactions in porphyrin dications implies that porphyrin-containing systems may display similar non-standard hydrogen bonding behavior in transient electronic states where the charge on the core is also high [ 60 ]. C–H⋯O interactions are not regularly observed in porphyrin molecules, salts, or complexes without additional charge.…”

Section: Resultsmentioning

confidence: 99%

Weak Interactions and Conformational Changes in Core-Protonated A2- and Ax-Type Porphyrin Dications

et al. 2020

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Individual chemical motifs are known to introduce structural distortions to the porphyrin macrocycle, be it in the core or at the periphery of the macrocycle. The interplay when introducing two or more of these known structural motifs has been scarcely explored and is not necessarily simply additive; these structural distortions have a chance to compound or negate to introduce new structural types. To this end, a series of compounds with complementary peripheral (5,15-disubstitution) and core (acidification) substitution patterns were investigated. The single-crystal X-ray structures of 18 5,15-diphenylporphyrin, 5,15-diphenylporphyrindi-ium diacid, and related compounds are reported, including the first example of a 5,15-dialkylporphyrindi-ium. Normal-coordinate structural decomposition (NSD) analysis is used for a detailed analysis of the conformation of the porphyrin subunit within the crystal structures. An elongation of porphyrin macrocycles along the C5,C15- axis (B2g symmetry) is observed in all of the free base porphyrins and porphyrin dications; distance across the core is around 0.3 Å in the free base and diacid compounds, and more than doubled in 5,15-dipentylporphyrin and 5,15-dipentylporphyrindi-ium diacid. While the free base porphyrins are largely planar, a large out-of-plane distortion can be observed in 5,15-diphenylporphyrin diacids, with the expected “projective saddle” shape characteristic for such systems. The combination of these two distortions (B2u and B2g) from regular porphyrin structure results in a macrocycle best characterized in the chiral point-group D2. A rare structural type of a cis-hydrogen bond chelate is observed for 5,15-dipentylporphyrindi-ium diacid, which adopts an achiral C2v symmetry. Crystallographic data indicate that the protonated porphyrin core forms hydrogen bonding chelates (N-H⋯X⋯H-N) to counter-anions. Weaker interactions, such as induced intramolecular C-H⋯O interactions from the porphyrin periphery are described, with distances characteristic of charge-assisted interactions. This paper offers a conceptual framework for accessing porphyrin macrocycles with designable distortion and symmetry, useful for the selective perturbation of electronic states and a design-for-application approach to solid state porphyrin materials.

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“…Moreover, electrostatic interactions like in heteroatom-hydrogen bonds X-H···Y (X = O or N; Y = O, N, or halogen), salt bridges, van der Waals interactions (π-π interactions), carbon–hydrogen, and metal interactions are required for the formation and stability of the protein–ligand complexes [ 68 , 69 , 70 ]. Especially, hydrogen bond is observed as an intermolecular interaction that exhibits covalent, electrostatic, and van der Waals properties [ 71 , 72 ] Therefore, hydrogen bonds not only mediate protein–ligand binding but also influence the physicochemical properties of the molecules, such as solubility, distribution, partitioning, and permeability, which are key characteristics for drug development [ 73 , 74 ].…”

Section: Resultsmentioning

confidence: 99%

Computational and In Vitro Investigation of (-)-Epicatechin and Proanthocyanidin B2 as Inhibitors of Human Matrix Metalloproteinase 1

et al. 2020

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Matrix metalloproteinases 1 (MMP-1) energetically triggers the enzymatic proteolysis of extracellular matrix collagenase (ECM), resulting in progressive skin aging. Natural flavonoids are well known for their antioxidant properties and have been evaluated for inhibition of matrix metalloproteins in human. Recently, (-)-epicatechin and proanthocyanidin B2 were reported as essential flavanols from various natural reservoirs as potential anti-inflammatory and free radical scavengers. However, their molecular interactions and inhibitory potential against MMP-1 are not yet well studied. In this study, sequential absorption, distribution, metabolism, and excretion (ADME) profiling, quantum mechanics calculations, and molecular docking simulations by extra precision Glide protocol predicted the drug-likeness of (-)-epicatechin (−7.862 kcal/mol) and proanthocyanidin B2 (−8.145 kcal/mol) with the least reactivity and substantial binding affinity in the catalytic pocket of human MMP-1 by comparison to reference bioactive compound epigallocatechin gallate (−6.488 kcal/mol). These flavanols in docked complexes with MMP-1 were further studied by 500 ns molecular dynamics simulations that revealed substantial stability and intermolecular interactions, viz. hydrogen and ionic interactions, with essential residues, i.e., His218, Glu219, His222, and His228, in the active pocket of MMP-1. In addition, binding free energy calculations using the Molecular Mechanics Generalized Born Surface Area (MM/GBSA) method suggested the significant role of Coulomb interactions and van der Waals forces in the stability of respective docked MMP-1-flavonol complexes by comparison to MMP-1-epigallocatechin gallate; these observations were further supported by MMP-1 inhibition assay using zymography. Altogether with computational and MMP-1–zymography results, our findings support (-)-epicatechin as a comparatively strong inhibitor of human MMP-1 with considerable drug-likeness against proanthocyanidin B2 in reference to epigallocatechin gallate.

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N+-C-H···O Hydrogen bonds in protein-ligand complexes

Cited by 118 publications

References 38 publications

The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations

The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations

Weak Interactions and Conformational Changes in Core-Protonated A2- and Ax-Type Porphyrin Dications

Computational and In Vitro Investigation of (-)-Epicatechin and Proanthocyanidin B2 as Inhibitors of Human Matrix Metalloproteinase 1

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