DNA Conformational Changes Research Articles

Enhancing DNA Translocation Performance and Conformational Changes in Quartz Nanopipettes by Ionic Liquid Modification

Enhancing DNA Translocation Performance and Conformational Changes in Quartz Nanopipettes by Ionic Liquid Modification

Conformational Changes in DNA and Protein Biomolecules in Pathogenesis of Ischemic Stroke.

Conformational changes in DNA and protein biomolecules were studied in ischemic stroke (IS) cases varying severity by Raman spectroscopy. The conformational structure of hematoporphyrin was found to change in IS patients, leading to a higher (I1355/I1550)/(I1375/I1580) ratio (hemoglobin affinity of for ligands) and an increase in I1375/I1172 (a change in pyrrole conformation). Changes in genomic DNA spectra were observed at frequencies caused by stretching vibrations of primary amines (3400 cm-1), secondary amines and hydroxyls involved in hydrogen bonding (3100 cm-1), and CH2 groups of sugar phosphates (2900 cm-1) and vibrations of vibrational bonds between nitrogenous bases and sugars (1400 cm-1). The significant changes observed in genomic DNA and hemoglobin spectra were assumed to indicate conformational rearrangements of the molecules in IS. Severe IS was associated with maximum changes in DNA and hemoglobin spectra.

An Insight into the Mechanism of DNA Cleavage by DNA Endonuclease from the Hyperthermophilic Archaeon Pyrococcus furiosus.

Hyperthermophilic archaea such as Pyrococcus furiosus survive under very aggressive environmental conditions by occupying niches inaccessible to representatives of other domains of life. The ability to survive such severe living conditions must be ensured by extraordinarily efficient mechanisms of DNA processing, including repair. Therefore, in this study, we compared kinetics of conformational changes of DNA Endonuclease Q from P. furiosus during its interaction with various DNA substrates containing an analog of an apurinic/apyrimidinic site (F-site), hypoxanthine, uracil, 5,6-dihydrouracil, the α-anomer of adenosine, or 1,N6-ethenoadenosine. Our examination of DNA cleavage activity and fluorescence time courses characterizing conformational changes of the dye-labeled DNA substrates during the interaction with EndoQ revealed that the enzyme induces multiple conformational changes of DNA in the course of binding. Moreover, the obtained data suggested that the formation of the enzyme-substrate complex can proceed through dissimilar kinetic pathways, resulting in different types of DNA conformational changes, which probably allow the enzyme to perform its biological function at an extreme temperature.

Integrative transcriptomic profiling of ncRNAs and mRNAs in developing mouse lens.

In recent years, burgeoning research has underscored the pivotal role of non-coding RNA in orchestrating the growth, development, and pathogenesis of various diseases across organisms. However, despite these advances, our understanding of the specific contributions of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) to lens development remains notably limited. Clarifying the intricate gene regulatory networks is imperative for unraveling the molecular underpinnings of lens-related disorders. In this study, we aimed to address this gap by conducting a comprehensive analysis of the expression profiles of messenger RNAs (mRNAs), lncRNAs, and circRNAs at critical developmental time points of the mouse lens, encompassing both embryonic (E10.5, E12.5, and E16.5) and postnatal stages (P0.5, P10.5, and P60). Leveraging RNA-sequencing technology, we identified key transcripts pivotal to lens development. Our analysis revealed differentially expressed (DE) mRNAs, lncRNAs, and circRNAs across various developmental stages. Particularly noteworthy, there were 1831 co-differentially expressed (CO-DE) mRNAs, 150 CO-DE lncRNAs, and 13 CO-DE circRNAs identified during embryonic stages. Gene Ontology (GO) enrichment analysis unveiled associations primarily related to lens development, DNA conformational changes, and angiogenesis among DE mRNAs and lncRNAs. Furthermore, employing protein-protein interaction networks, mRNA-lncRNA co-expression networks, and circRNA-microRNA-mRNA networks, we predicted candidate key molecules implicated in lens development. Our findings underscore the pivotal roles of lncRNAs and circRNAs in this process, offering fresh insights into the pathogenesis of lens-related disorders and paving the way for future exploration in this field.

Skipping events impose repeated binding attempts: profound kinetic implications of protein-DNA conformational changes.

The kinetics of protein-DNA recognition, along with its thermodynamic properties, including affinity and specificity, play a central role in shaping biological function. Protein-DNA recognition kinetics are characterized by two key elements: the time taken to locate the target site amid various nonspecific alternatives; and the kinetics involved in the recognition process, which may necessitate overcoming an energetic barrier. In this study, we developed a coarse-grained (CG) model to investigate interactions between a transcription factor called the sex-determining region Y (SRY) protein and DNA, in order to probe how DNA conformational changes affect SRY-DNA recognition and binding kinetics. We find that, not only does a requirement for such a conformational DNA transition correspond to a higher energetic barrier for binding and therefore slower kinetics, it may further impede the recognition kinetics by increasing unsuccessful binding events (skipping events) where the protein partially binds its DNA target site but fails to form the specific protein-DNA complex. Such skipping events impose the need for additional cycles protein search of nonspecific DNA sites, thus significantly extending the overall recognition time. Our results highlight a trade-off between the speed with which the protein scans nonspecific DNA and the rate at which the protein recognizes its specific target site. Finally, we examine molecular approaches potentially adopted by natural systems to enhance protein-DNA recognition despite its intrinsically slow kinetics.

Macromolecules with predominant β-pleated sheet proteins in extracellular vesicles released from Raphanus sativus L. var. caudatus Alef microgreens induce DNA damage-mediated apoptosis in HCT116 colon cancer cells

Plant-derived bioactive macromolecules (i.e., proteins, lipids, and nucleic acids) were prepared as extracellular vesicles (EVs). Plant-derived EVs are gaining pharmaceutical research interest because of their bioactive components and delivery properties. The spherical nanosized EVs derived from Raphanus sativus L. var. caudatus Alef microgreens previously showed antiproliferative activity in HCT116 colon cancer cells from macromolecular compositions (predominantly proteins). To understand the mechanism of action, the biological activity studies, i.e., antiproliferation, cellular biochemical changes, DNA conformational changes, DNA damage, apoptotic nuclear morphological changes, apoptosis induction, and apoptotic pathways, were determined by neutral red uptake assay, synchrotron radiation-based Fourier transform infrared microspectroscopy, circular dichroism spectroscopy, comet assay, 4′,6-diamidino-2-phenylindole (DAPI) staining, flow cytometry, and caspase activity assay, respectively. EVs inhibited HCT116 cell growth in concentration- and time-dependent manners, with a half-maximal inhibitory concentration of 675.4 ± 33.8 μg/ml at 48 h and a selectivity index of 1.5 ± 0.076. HCT116 treated with EVs mainly changed the cellular biochemical compositions in the nucleic acids and carbohydrates region. The DNA damage caused no changes in DNA conformation. The apoptotic nuclear morphological changes were associated with the increased apoptotic cell population. The apoptotic cell death was induced by both extrinsic and intrinsic pathways. EVs have potential as antiproliferative bioparticles.

Assessment of the electrostatic binding of ferrocenylmethyl-nitroaniline derivatives to DNA: A combined experimental and theoretical study

The present study investigates the electrostatic binding interactions between ferrocenylmethylnitroaniline derivatives and DNA using a combination of experimental and theoretical approaches. The objective is to elucidate the binding mechanisms and evaluate the potential of these derivatives as DNA-targeting agents. Experimental techniques, including cyclic voltammetry (CV) and UV–Vis spectroscopy (UV–Vis), were employed to assess the binding affinity and conformational changes in DNA upon interaction with the derivatives. Our findings reveal that the ferrocenylmethylnitroaniline derivatives exhibit strong electrostatic interactions with DNA, as confirmed by the negative formal potential shift observed in CV. The binding constants and free binding energies obtained from the docking simulation were found to be consistent with those obtained from CV and UV–Vis spectral analysis. Furthermore, the binding site size was determined from the voltametric data. Complementary theoretical calculations such as geometry optimization, MEP analysis, Mulliken charge distribution, and HOMO-LUMO surface were performed by DFT approach (B3LYP/aug-cc-pVTZ/6-311++G (d,p)) to gain insights into the structural data, active regions, and chemical reactivity of derivatives. Molecular docking simulation verifies that electrostatic attraction plays a fundamental role in the interaction of Fc2N, Fc3N, and Fc4N with DNA. The molecular dynamics simulations elucidated the stability of DNA-ligand complexes formed with Fc2N, Fc3N, and Fc4N compounds. Analysis of root mean square deviation (RMSD) and radius of gyration (Rg) indicated stable binding and maintained compactness of DNA structures, underscoring the robustness of these interactions for potential therapeutic applications.Top of Form

Synergistic effects and competitive relationships between DOC and DOX as acting on DNA molecules: Studied with confocal Raman spectroscopy and molecular docking technology

Docetaxel (DOC) is one of the second-generation antineoplastic drugs of the taxanes family with excellent antitumor activity. However, the mechanism of DOC inducing tumor cell apoptosis and treating cancer diseases, especially its interaction with DNA in the nucleus, and its adjuvant or combined Doxorubicin (DOX) acting on DNA molecules are unclear. In this study, the interaction mechanism between DOC and DNA, as well as the synergistic effects and competitive relationships among DOC and DOX when they simultaneously interact with DNA molecules were studied by laser confocal Raman spectroscopy combined with UV–visible absorption spectroscopy and molecular docking technology. The spectroscopic results showed that the binding constant of DOC to DNA is 5.25 × 103 M−1, the binding modes of DOC and DNA are non-classical intercalation and electrostatic binding, and the DNA-DOC complex has good stability. When DOC or DOX interacts with DNA alone, both of them can bind with bases and phosphate backbone of DNA, and also lead to DNA conformation changes; when DOC and DOX interact with DNA at the same time, the orders of interaction not only affect their binding sites with DNA, but also cause changes in the surrounding environment of the binding sites. In addition, the molecular docking results further verified that DOC and DOX have synergy and competition when they interact with DNA molecules simultaneously. The docking energies of DNA-DOC and DNA-DOX indicate the important role of van der Waals forces and hydrogen bonds. This study has practical significance for the design and development of antitumor drugs with less toxic based on the taxanes family and the combination with other drugs for the treatment of cancer.

An ATP-free packaging of T4 DNA

Packaging of viral DNA into a capsid with liquid crystalline density is a crucial step in viral reproduction. DNA packaging with an adenosine triphosphate (ATP)-fueled molecular motor is an established viral DNA packaging mechanism system. On the other hand, DNA is compacted by the conformational change attributable to multivalent cations exclusively at valences higher than three. The conformational change of DNA was not considered as a mechanism of DNA packaging of viruses. Here, T4 DNA, ejected from a capsid in the ambient concentration of phosphate corresponding to the intra-cell concentration, is packaged into the capsid when the phosphate concentration decreases to the extra-cell concentration in coexistence with divalent cations, that is, Ca2+ and Mg2+. The compaction and packaging processes coincide with the conformational change of DNA. Divalent cations can compact T4 DNA when the counter anion is phosphate. The DNA-packaged and re-generated virions showed equivalent infective ability with the original populations. Fluorescent microscopy distinguished the conformational changes of DNA between compact forms and coil forms. Packaged or unpackaged DNA was confirmed enzymatically. Plaque-forming unit (Pfu) was used as the measure of infectious ability of virions. The concentration of ATP was measured by the luminometric method. The packaging process was proceeded in picomolar or lower concentration of ATP. This series of procedures may constitute a new ATP-free or low-ATP approach to packaging viral DNA with DNA conformational change underpinning the process. The results from this study may disclose an undiscovered facet of T4 life cycle.

Long-term, non-invasive FTIR detection of low-dose ionizing radiation exposure

Non-invasive methods of detecting radiation exposure show promise to improve upon current approaches to biological dosimetry in ease, speed, and accuracy. Here we developed a pipeline that employs Fourier transform infrared (FTIR) spectroscopy in the mid-infrared spectrum to identify a signature of low dose ionizing radiation exposure in mouse ear pinnae over time. Mice exposed to 0.1 to 2 Gy total body irradiation were repeatedly measured by FTIR at the stratum corneum of the ear pinnae. We found significant discriminative power for all doses and time-points out to 90 days after exposure. Classification accuracy was maximized when testing 14 days after exposure (specificity > 0.9 with a sensitivity threshold of 0.9) and dropped by roughly 30% sensitivity at 90 days. Infrared frequencies point towards biological changes in DNA conformation, lipid oxidation and accumulation and shifts in protein secondary structure. Since only hundreds of samples were used to learn the highly discriminative signature, developing human-relevant diagnostic capabilities is likely feasible and this non-invasive procedure points toward rapid, non-invasive, and reagent-free biodosimetry applications at population scales.

Involvement of Histone Acetyltransferase 1 (HAT1) in the Spermatogenesis of Non-Condensed Nuclear Sperm in Chinese Mitten Crab, Eriocheir sinensis.

Chinese mitten crab, Eriocheir sinensis, is a decapod crustacean with a special, non-condensated nucleus in the sperm. Studies have shown that the nuclear compact state of male germ cells during the spermatogenesis is closely related to histone modification. To explore the possible role of histone acetyltransferase 1 (HAT1) in the chromatin organization during the E. sinensis spermatogenesis, we took the testis tissues of both adult and juvenile crabs as the materials of study and analyzed the biological functions of HAT1 by whole transcriptome sequencing and bioinformatics, then further analyzed the expression and distribution of HAT1 using the methods of RT-qRCR, western blotting, and immunofluorescence location. The results showed that HAT1 is an alkaline-unstable hydrophilic protein. Itwaspredictedtointeractwith a variety of histones and chromosome assembly proteins, including Asf1b, Chaf1b, and Hist1h3f, and is involved in many biological functions pertaining to chromatin dynamics such as chromatin organization, DNAdependent nucleosome assembly, DNA conformational changes, and so on. HAT1 was up-regulated in the adult testes compared to the juvenile (n = 3, P < 0.05). HAT1 was mainly located in the nuclei of male germ cells of E. sinensis. As spermatogenesis proceeded, the expression of HAT1 decreased and evendisappearedinthenuclei (n = 3, P < 0.05). HAT1 is an important player in histone acetylation, which facilitates chromatin alteration in a three-dimensional conformation. The expression of HAT1 in different male germ cells might indicate the chromatin dynamics at the diversity stages of spermatogenesis. The high expression of HAT1 at the early stages of E. sinensis spermatogenesis hints the active involvement in chromatin organization, while its progressively reduced expression accompanied by the progression of spermatogenesis suggests a relatively gradual stabilization and stereotyping of chromatin. As for the disappearance of HAT1 in mature sperm with non-condensed nuclei, the reduction in histones targeted by HAT1 or histone acetylation may be an important initiator.

Dynamic Insights into DNA Conformational Changes and the Impact of Magnesium Ions on Topoisomerase IA Enzymes: A Molecular Dynamics Simulation Study

Molecular dynamics simulations were employed to scrutinize the conformational changes in DNA strands and elucidate the influence of magnesium ions on Topoisomerase IA enzymes. Through the computation of Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), hydrogen bond distances, dihedral angles, and Solvated Accessible Surface Area (SASA), we meticulously examined the structural dynamics. The results reveal intricate patterns of DNA strand alterations, showcasing the profound role of magnesium ions in modulating the behavior of Topoisomerase IA enzymes. This study contributes essential insights into the molecular mechanisms governing DNA conformational changes, offering a foundation for further understanding the biochemical intricacies of Topoisomerase IA enzyme function.

DNA conformational change embrace ultraviolet photolysis: A dual-mode sensing platform for electrochemical and fluorescent signaling

We developed a dual-mode biosensor that utilizes DNA conformational changes and ultraviolet photolysis for electrochemical (EC) and fluorescence (FL) detection. In this study, a stem-loop-structured carcinoembryonic antigen (CEA) aptamer was modified on an Au electrode, and this aptamer contained a redox-labeled methylene blue (MB), short-chain DNA with a 6-carboxylic fluorescein (FAM) and a PC linker that can be cleaved by ultraviolet light. Subsequently, CEA and CEA antibody-modified upconversion nanoparticle bioconjugates (CEA-Ab@UCNPs) were added. In the presence of CEA, Ab@UCNPs can bind CEA and push the MB which was originally close to the electrode surface, away from the electrode surface, resulting in a reduced redox current. Under irradiation with a 980 nm laser, the UCNPs emit ultraviolet light, leading to photocleavage of the PC linker and the release of FAM for FL sensing. Under optimal conditions, the EC and FL modes showed good responses to CEA within 0.01–50 ng/mL and 0.1–80 ng/mL, respectively.

Mononuclear copper(II) complexes with polypyridyl ligands: synthesis, characterization, DNA interactions/cleavages and in vitro cytotoxicity towards human cancer cells.

DNA being the necessary element in cell regeneration, controlled cellular apoptosis via DNA binding/cleaving is considered an approach to combat cancer cells. The widely prescribed metallodrug cisplatin has shown interactions with the guanine-N7 center, and a plethora of complexes are continually developed to enhance crosslinking properties as well as covalent and non-covalent interactions. Two pentadentate ligands, L1 (1-(6-(1H-benzo[d]imidazol-2-yl)pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine) and L2 (1-(6-(1-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine), were synthesized together with their respective copper(II) complexes [1](ClO4)2 and [2](ClO4)2, which crystallized in a trigonal bipyramidal fashion. Different analytical and spectroscopic methods confirmed their formation, and their redox behaviour was also examined. The interactions of salmon sperm DNA (ss-DNA) with these two complexes were explored using absorbance spectroscopy, and they both exhibited a binding affinity (Kb) of ∼104 M-1. Fluorescence quenching experiments with ethidium bromide (EB)-bound DNA (EB-DNA) were also performed, and Stern-Volmer constant (KSV) values of 6.93 × 103 and 2.34 × 104 M-1 for [1](ClO4)2 and [2](ClO4)2, respectively, were obtained. Furthermore, DNA conformational changes due to the interactions of both complexes were validated via circular dichroism. We also assessed the DNA cleavage property of these complexes, which resulted in the linearization of circular plasmid DNA. This finding was supported by studying the growth of MDA-MB-231 breast cancer cells upon treatment with both Cu(II) complexes; IC50 values of 5.34 ± 1.02 μM and 0.83 ± 0.18 μM were obtained for [1](ClO4)2 and [2](ClO4)2, respectively. This validates their affinity towards DNA, and these insights can be further utilized for non-platinum based economical metallodrug development based on first row transition metals.

Validation of a Proteomic-Based Prognostic Model for Breast Cancer and Immunological Analysis.

Breast cancer (BC) has emerged as an extremely destructive malignancy, causing significant harm to female patients and society at large. Proteomic research holds great promise for early diagnosis and treatment of diseases, and the integration of proteomics with genomics can offer valuable assistance in the early diagnosis, treatment, and improved prognosis of BC patients. In this study, we downloaded breast cancer protein expression data from The Cancer Genome Atlas (TCGA) and combined proteomics with genomics to construct a proteomic-based prognostic model for BC. This model consists of nine proteins (HEREGULIN, IDO, PEA15, MERIT40_pS29, CIITA, AKT2, CD171 DVL3, and CABL9). The accuracy of the model in predicting the survival prognosis of BC patients was further validated through risk curve analysis, survival curve analysis, and independent prognostic analysis. We further confirmed the impact of differential expression of these nine key proteins on overall survival in BC patients, and the differential expression of the key proteins and their encoding genes was validated using immunohistochemical staining. Enrichment analysis revealed functional associations primarily related to PPAR signaling pathway, steroid hormone metabolism, chemokine signaling pathway, DNA conformation changes, immunoglobulin production, and immunoglobulin complex in the high- and low-risk groups. Immune infiltration analysis revealed differential expression of immune cells between the high- and low-risk groups, providing a theoretical basis for subsequent immunotherapy. The model constructed in this study can predict the survival of BC patients, and the identified key proteins may serve as biomarkers to aid in the early diagnosis of BC. Enrichment analysis and immune infiltration analysis provide a necessary theoretical basis for further exploration of the molecular mechanisms and subsequent immunotherapy.

4mC-CGRU: Identification of N4-Methylcytosine (4mC) sites using convolution gated recurrent unit in Rosaceae genome

An epigenetic modification is DNA N4-methylcytosine (4mC) that affects several biological functions without altering the DNA nucleotides, including DNA conformation, cell development, replication, stability, and DNA structural changes. To prevent restriction enzyme from damaging self-DNA, 4mC performs a critical role in restriction–modification functions. Existing studies mainly focused on finding hand-crafted features to identify 4mC locations, but these methods are inefficient due to high time consuming and high costs. In our research work, we propose a 4mC-CGRU which is a deep learning-based computational model with a standard encoding method to identify the 4mC sites from DNA sequences that learned autonomous feature selection in the Rosaceae genome, particularly in Rosa chinensis (R. chinensis) and Fragaria vesca (F. vesca). The proposed model consists of a convolutional neural network (CNN) and a gated recurrent unit network (GRU)-based model for identifying 4mC sites from Fragaria vesca and Rosa chinensis in the genomes. The CNN model extracts useful features from the datasets and the GRU classifies the DNA sequences. Thus, our approach can automatically extract important features to detect relative sites from DNA sequence. The performance analysis shows that the proposed model consistently outperforms over the state-of-the-art works in detecting 4mC sites.

Structural changes in DNA by binding mitochondrion-targeted monofunctional platinum(II) complexes using molecular dynamics simulation study

Triphenylphosphonium (Ph3P+, TPP) is a highly effective mitochondrial targeting group, an example of using which on mitochondrion-targeted monofunctional platinum(II) agent as anticancer drug was OPT, with the –CH2Ph3P+ group at ortho position of the pyriplatin pyridine ring. To study how carrier ligands might affect the efficacy of OPT, we constructed two platinum(II) agents with bulky bidentate ligands based on OPT. DNA structural changes caused by these three platinum(II) agents using molecular dynamics simulations were analysed. Data regarding DNA conformational changes including helical parameter, base stacking, average structure, and principal component analyses has been obtained. We found that TPP-based monofunctional platinum(II) complexes with bulky carrier ligands may induce more significant DNA conformational changes. These results are beneficial for developing highly efficient mitochondrion-targeted platinum anticancer drugs with carrier ligands of different steric hindrance.

Super enhancer-driven core transcriptional regulatory circuitry crosstalk with cancer plasticity and patient mortality in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer. Core transcriptional regulatory circuitry (CRC) consists of autoregulated transcription factors (TFs) and their enhancers, which dominate gene expression programs and control cell fate. However, there is limited knowledge of CRC in TNBC. Herein, we systemically characterized the activated super-enhancers (SEs) and interrogated 14 CRCs in breast cancer. We found that CRCs could be broadly involved in DNA conformation change, metabolism process, and signaling response affecting the gene expression reprogramming. Furthermore, these CRC TFs are capable of coordinating with partner TFs bridging the enhancer-promoter loops. Notably, the CRC TF and partner pairs show remarkable specificity for molecular subtypes of breast cancer, especially in TNBC. USF1, SOX4, and MYBL2 were identified as the TNBC-specific CRC TFs. We further demonstrated that USF1 was a TNBC immunophenotype-related TF. Our findings that the rewiring of enhancer-driven CRCs was related to cancer immune and mortality, will facilitate the development of epigenetic anti-cancer treatment strategies.

Chitosan polyplexes: Energetics of formation and conformational changes in DNA upon binding and release

Energetics of chitosan (CS) polyplexes and conformational stability of bound DNA were studied at pH 5.0 by ITC and HS–DSC, respectively. The CS–DNA binding isotherm was well approximated by the McGhee–von Hippel model suggesting the binding mechanism to be a cooperative attachment of interacting CS ligands to the DNA matrix. Melting thermograms of polyplexes revealed the transformation of different conformational forms of bound DNA in dependence on the CS/DNA weight ratio rw. At 0<rw<0.7 two conformational forms were observed and assigned, respectively, to the intact (free) and globular (bound) DNA. A contribution of the globular DNA to the melting enthalpy approached 100 % at the equivalent weight CS content. At higher CS contents a further stabilization of the globular DNA conformation was detected and assigned to the DNA globules in overcharged polyplexes. The polyplex dissociation was studied at pH 7.4 under conditions of zero and a physiological concentration of NaCl. Phase separation of the system was observed in both cases. DNA was almost completely immobilized in the lower phase enriched with CS. At physiological ionic strength, DNA converted from the globular to the intact form although remained to be immobilized in the CS phase.

An analysis of interactions between three structurally diverse anthocyanidins, as well as their glucosides, and model biological membranes, albumin, and plasmid DNA

The aim of the study is to investigate the differences in the interaction of three structurally diverse anthocyanidins, namely peonidin, petunidin, and delphinidin, as well as their glucosides with model biological membranes, human albumin, and plasmid DNA in order to look into their structure–activity relationships. Fluorimetric studies, as well as ATR-FTIR analyses, were jointly used in order to determine the changes observed in both the hydrophilic and hydrophobic layers of cell-mimic membranes (MM) which reflected the membrane lipid composition of tumour cells and red blood cell membranes (RBCM). Our results showed that anthocyanins and anthocyanidins can cause an increase in the packing order of the polar heads of lipids, as well as interact with their deeper layers by reducing the fluidity of lipid chains. The results presented here indicate that all compounds tested here possessed the ability to bind to human serum albumin (HSA) and the presence of a glucose molecule within the structures formed by anthocyanidin reduces their ability to bind to proteins. Using fluorescence correlation spectroscopy, it was demonstrated that the compounds tested here were capable of forming stable complexes with plasmid DNA and, particularly, strong DNA conformational changes were observed in the presence of petunidin and corresponding glucoside, as well as delphinidin. The results we obtained can be useful in comprehending the anthocyanins therapeutic action as molecular antioxidants and provide a valuable insight into their mechanism of action.