Computational DNA binding studies of (–)-epigallocatechin-3-gallate

Abstract

The catechin family of molecules that are present in the leaves of green tea has been under investigation since the antioxidant and anti-inflammatory properties of tea were discovered. Among multiple proposed therapeutic targets of these molecules, the direct interaction with nucleic acids has been proposed and experimentally observed but without clear knowledge about the potential binding modes between these ligands and DNA. One of these catechin structures, (-)-epigallocatechin gallate (EGCG), has three aromatic rings that could interact with double-stranded DNA via terminal base-pair stacking, intercalation, or through groove binding. Using enhanced sampling techniques and molecular dynamics simulations, we have found a stable complex between the EGCG ligand and DNA through intercalation of the trihydroxybenzoate aromatic ring and an ApC step. Moreover, we have calculated the absorption spectra of four possible binding modes and compared these to absorption profiles reported in the literature, and explored the possible DNA sequence preference for the EGCG ligand to bind. Our results suggest that an intercalative mode of interaction through the major groove is possible between the EGCG ligands and DNA with apparently very little DNA sequence selectivity.

Gelatin‐Encapsulated Tetrahedral DNA Nanostructure Enhances Cellular Internalization for Treating Noise‐Induced Hearing Loss

“…EGCG can intercalate into double‐stranded DNA through non‐covalent interactions between the phenolic groups of EGCG and the phosphate backbone of DNA helices. [ 47,48 ] Similar interactions take place between dsDNA and other compounds such as flavonoids and quinones. [ 49,50 ] The loading of EGCG slightly increased the hydrodynamic diameter of TDNs (from 15 to 18 nm), with minimal impact on their zeta potential of approximately −11 mV.…”

Engineering polyphenol-based carriers for nucleic acid delivery

“…Fujiki et al found that single-strand 18 mers of DNA or RNA could bind to 1 to 3 EGCG molecules in surface plasmon resonance assay (Biacore) and cold spray ionization-mass spectrometry, suggesting that multiple binding sites of EGCG were present in DNA and RNA oligomers 64 . Using enhanced sampling techniques and molecular dynamics simulations, Rodrigo et al observed that both benzopyran moiety ring and trihydroxyphenyl ring of EGCG could form hydrogen bonds with the oxygen atoms in the DNA backbone of the 5'-strand, and a stable complex was formed between the EGCG ligand and DNA by intercalating the trihydroxybenzoate aromatic ring and an ApC step 65 . In summary, the interactions between polyphenols and nucleic acids are synergistically mediated by both intermolecular hydrogen bonds and hydrophobic interactions, which are the basic mechanism of building polyphenol-assisted drug delivery systems.…”

Epigallocatechin gallate-loaded tetrahedral DNA nanostructures as a novel inner ear drug delivery system

“…To further explore the potential of TDNs for inner ear drug delivery, EGCG, a double-stranded DNA intercalator with antioxidant activity, was loaded into TDNs. 39,40 The morphologies and zeta potentials of TDNs and EGCG@TDNs were characterized. Uniform morphologies of TDNs and EGCG@TDNs, with minimal size difference, were observed by TEM imaging (Fig.…”