An Investigation into the Interaction between Double Hydroxide-Based Antioxidant Benzophenone Derivatives and Cyclooxygenase 2

Cyclooxygenases 2 (COX2) is a therapeutic target for many inflammation and oxidative stress associated diseases. A high-throughput technique, biolayer interferometry, was performed to primarily screen the potential COX2 binding activities of twelve newly synthesized double hydroxide-based benzophenone derivatives. Binding confirmation was achieved by molecular docking and multi-spectroscopy studies. Such a combined method provided a comprehensive understanding of binding mechanism and conformational changes. Compounds DB2, SC2 and YB2 showed effective COX2 binding activity and underlined the benefits of three phenolic hydroxyl groups adjacent to each other on the B ring. The twelve tested derivatives were further evaluated for antioxidant activity, wherein compound SC2 showed the highest activity. Its concentration for the 50% of maximal effect (EC50) value was approximately 1000 times greater than that of the positive controls. SC2 treatment effectively improved biochemical indicators caused by oxidative stress. Overall, compound SC2 could serve as a promising candidate for further development of a new potent COX2 inhibitor.

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Reactivity of Aliphatic and Phenolic Hydroxyl Groups in Kraft Lignin towards 4,4′ MDI

Molecules ◽

10.3390/molecules26082131 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2131

Author(s):

Leonardo Dalseno Antonino ◽

Júlia Rocha Gouveia ◽

Rogério Ramos de Sousa Júnior ◽

Guilherme Elias Saltarelli Garcia ◽

Luara Carneiro Gobbo ◽

...

Keyword(s):

Experimental Work ◽

Chemical Structure ◽

31P Nmr ◽

Kraft Lignin ◽

Hydroxyl Group ◽

Hydroxyl Groups ◽

Diphenylmethane Diisocyanate ◽

Complex Chemical ◽

Heterogeneous Reactivity ◽

Phenolic Hydroxyl Groups

Several efforts have been dedicated to the development of lignin-based polyurethanes (PU) in recent years. The low and heterogeneous reactivity of lignin hydroxyl groups towards diisocyanates, arising from their highly complex chemical structure, limits the application of this biopolymer in PU synthesis. Besides the well-known differences in the reactivity of aliphatic and aromatic hydroxyl groups, experimental work in which the reactivity of both types of hydroxyl, especially the aromatic ones present in syringyl (S-unit), guaiacyl (G-unit), and p-hydroxyphenyl (H-unit) building units are considered and compared, is still lacking in the literature. In this work, the hydroxyl reactivity of two kraft lignin grades towards 4,4′-diphenylmethane diisocyanate (MDI) was investigated. 31P NMR allowed the monitoring of the reactivity of each hydroxyl group in the lignin structure. FTIR spectra revealed the evolution of peaks related to hydroxyl consumption and urethane formation. These results might support new PU developments, including the use of unmodified lignin and the synthesis of MDI-functionalized biopolymers or prepolymers.

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Conformational changes in the chicken receptor for endocytosis of glycoproteins. Modulation of ligand-binding activity by Ca2+ and pH.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)81582-x ◽

1988 ◽

Vol 263 (20) ◽

pp. 9752-9760

Author(s):

J A Loeb ◽

K Drickamer

Keyword(s):

Ligand Binding ◽

Conformational Changes ◽

Binding Activity ◽

Ligand Binding Activity

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Structure of the p53/RNA polymerase II assembly

Communications Biology ◽

10.1038/s42003-021-01934-4 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Shu-Hao Liou ◽

Sameer K. Singh ◽

Robert H. Singer ◽

Robert A. Coleman ◽

Wei-Li Liu

Keyword(s):

Dna Binding ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Conformational Changes ◽

P53 Protein ◽

Binding Activity ◽

Transactivation Domain ◽

Pol Ii ◽

Dna Binding Activity ◽

Regulated Gene Expression

AbstractThe tumor suppressor p53 protein activates expression of a vast gene network in response to stress stimuli for cellular integrity. The molecular mechanism underlying how p53 targets RNA polymerase II (Pol II) to regulate transcription remains unclear. To elucidate the p53/Pol II interaction, we have determined a 4.6 Å resolution structure of the human p53/Pol II assembly via single particle cryo-electron microscopy. Our structure reveals that p53’s DNA binding domain targets the upstream DNA binding site within Pol II. This association introduces conformational changes of the Pol II clamp into a further-closed state. A cavity was identified between p53 and Pol II that could possibly host DNA. The transactivation domain of p53 binds the surface of Pol II’s jaw that contacts downstream DNA. These findings suggest that p53’s functional domains directly regulate DNA binding activity of Pol II to mediate transcription, thereby providing insights into p53-regulated gene expression.

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Horseradish peroxidase-catalyzed formation of hydrogels from chitosan and poly(vinyl alcohol) derivatives both possessing phenolic hydroxyl groups

Carbohydrate Polymers ◽

10.1016/j.carbpol.2014.05.010 ◽

2014 ◽

Vol 111 ◽

pp. 404-409 ◽

Cited By ~ 25

Author(s):

Shinji Sakai ◽

Mehdi Khanmohammadi ◽

Ali Baradar Khoshfetrat ◽

Masahito Taya

Keyword(s):

Horseradish Peroxidase ◽

Vinyl Alcohol ◽

Phenolic Hydroxyl ◽

Poly Vinyl Alcohol ◽

Hydroxyl Groups ◽

Phenolic Hydroxyl Groups

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Hematin is an Alternative Catalyst to Horseradish Peroxidase for In Situ Hydrogelation of Polymers with Phenolic Hydroxyl Groups In Vivo

Biomacromolecules ◽

10.1021/bm100623k ◽

2010 ◽

Vol 11 (8) ◽

pp. 2179-2183 ◽

Cited By ~ 21

Author(s):

Shinji Sakai ◽

Kousuke Moriyama ◽

Kenichi Taguchi ◽

Koei Kawakami

Keyword(s):

Horseradish Peroxidase ◽

Phenolic Hydroxyl ◽

Hydroxyl Groups ◽

Phenolic Hydroxyl Groups

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The apparent ionization constants of the phenolic hydroxyl groups of thyroxine and related compounds

Archives of Biochemistry and Biophysics ◽

10.1016/0003-9861(55)90048-5 ◽

1955 ◽

Vol 54 (2) ◽

pp. 359-367 ◽

Cited By ~ 89

Author(s):

Chalmers L. Gemmill

Keyword(s):

Phenolic Hydroxyl ◽

Ionization Constants ◽

Hydroxyl Groups ◽

Phenolic Hydroxyl Groups ◽

Related Compounds

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Overlap of IGF- and heparin-binding sites in rat IGF-binding protein-5

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0240043 ◽

2000 ◽

Vol 24 (1) ◽

pp. 43-51 ◽

Cited By ~ 26

Author(s):

H Song ◽

J Beattie ◽

IW Campbell ◽

GJ Allan

Keyword(s):

Binding Site ◽

Conformational Changes ◽

Binding Protein ◽

Binding Activity ◽

Binding Domain ◽

Site Directed Mutagenesis ◽

Heparin Binding ◽

Igf I ◽

Heparin Binding Domain ◽

Igf Binding

Using site-directed mutagenesis, we have undertaken a study of a potential IGF-binding site in the C-terminal domain of rat IGFBP-5, lying close to or within a previously described heparin-binding domain (residues 201-218) in this protein. After analysis of binding activity using three different methods - ligand blotting, solution phase equilibrium binding and biosensor measurement of real-time on- and off-rates - we report that the mutation of two highly conserved residues within this region (glycine 203 and glutamine 209) reduces the affinity of the binding protein for both IGF-I and IGF-II, while having no effect on heparin binding. In addition, we confirm that mutation of basic residues within the heparin-binding domain (R201L, K202E, K206Q and R214A) results in a protein that has attenuated heparin binding but shows only a small reduction in affinity for IGF-I and -II. Previous findings have described the reduction in affinity of IGFBP-5 for IGFs that occurs after complexation of the binding protein with heparin or other components of the extracellular matrix (ECM) and have postulated that such an interaction may result in conformational changes in protein structure, affecting subsequent IGF interaction. Our data suggesting potential overlap of heparin- and IGF-binding domains argue for a more direct effect of ECM modulation of the affinity of IGFBP-5 for ligand by partial occlusion of the IGF-binding site after interaction with ECM.

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