Insight into the role of the chemical nature and length of the loop nucleobases in the folding of G-quadruplex by the antimalarial drugs at the DNA interface.

G-quadruplexes (G4) have been proposed as an alternative target for cancer therapy, as the folding of DNA sequences into stabilized G4 in the cancer microenvironment affects key biological functions. The antimalarial drugs, hydroxychloroquine (HCQ) and chloroquine (CQ), are in the clinical trial stage for cancer therapy and have been found to fold DNA sequences into the stabilized G4 even in the absence of KCl salt. In this study, the role of loop nucleobases in terms of chemical nature, number, and location in the HCQ-/CQ-induced folding of DNA sequences into G4 in the absence of KCl has been investigated systematically.

Nucleobase Level Information into the Folding of G-Quadruplex by Anti-inflammatory Drugs in the Absence of Salt.

G-quadruplexes (G4s) in the telomere region are important targets for cancer therapy. Molecules that can fold and stabilize the telomere DNA sequences, even in the absence of salt, can be an exciting prospect for therapy purposes. Anti-inflammatory drugs hydroxychloroquine (HCQ) and chloroquine (CQ) have shown promising effects in cancer therapy and also in the different levels of trial stages.

Flanking Effect on the Folding of Telomeric DNA Sequences into G-Quadruplex Induced by Antimalarial Drugs.

The folding of the guanine repetitive region in the telomere unit into G-quadruplex (G4) by drugs has been suggested as an alternative approach for cancer therapy. Hydroxychloroquine (HCQ) and chloroquine (CQ) are two important drugs in the trial stage for cancer. Both drugs can induce the folding of telomere-guanine-rich sequences into G4 even in the absence of salt.

Ionic Liquids-Induced Recovery of the G-Quadruplex DNA Destabilized by Dodine Fungicide.

Dodine is an important surfactant-based chemical fungicide used widely to kill fungi associated with black spot and foliar diseases on several fruit plants, such as apples, pears, peaches, and strawberries. However, the extensive use of dodine depicts the genotoxic effect, which may cause gene-associated diseases. Dodine can destabilize G-quadruplex (G4) DNA, which is one of the key targets for cancer therapy.

Flanking Effect on the Structure and Stability of Human Telomeric G-Quadruplex in Varying Salt Concentrations.

The stability of the human telomere G-quadruplex (G4) is directly linked to cancer disease. The human telomere is mostly associated with the flanking nucleobases, which can affect the stability of G4. Hence, in this study, the effect of the flanking nucleobases in the context of their chemical nature, number, and position on the structure and stability of G4 has been investigated in varying concentrations of KCl mimicking the normal and cancer KCl microenvironments.

Loop nucleobases-dependent folding of G-quadruplex in normal and cancer cell-mimicking KCl microenvironments.

In this study, the folding of G-quadruplex (G4) from the telomeric DNA sequences having loop nucleobases of different chemical natures, numbers, and arrangements in 10 mM and 100 mM KCl salt conditions mimicking the cancerous and normal KCl salt microenvironments have been investigated. The data suggest that the structure and stability of the G4 are highly dependent on the KCl salt concentration. In general, the conformational flexibility of the folded G4 is higher in KCl salt relevant to cancer than in the normal case for any loop arrangements with the same number of nucleobases.

Hydrophobic Interaction-Induced Topology-Independent Destabilization of G-Quadruplex.

Since the inception of the G-quadruplex (G4), enormous attention has been devoted to designing small molecules which can stabilize the G-quadruplex. In contrast, the knowledge about the molecules and mechanisms involved in the destabilization of G4 is sparse, although it is well recognized that destabilization of G4 is important in neurobiology and age-related genetic issues. In this study, it has been shown that amphiphilic molecules having a long hydrocarbon chain can destabilize G4, regardless of its topology, using various biophysical and molecular dynamics simulation methods.

Antimalarial Drugs Induce the Selective Folding of Human Telomeric G-Quadruplex in a Cancer-Mimicking Microenvironment.

Regulating the equilibrium between the duplex form of DNA and G-quadruplex (Gq) and stabilizing the folded Gq are the critical factors for any drug to be effective in cancer therapy due to the direct involvement of Gq in controlling the transcription process. Antimalarial drugs are in the trial stage for different types of cancer diseases; however, the plausible mechanism of action of these drug molecules is not well known. Hence, we investigate the plausible role of antimalarial drugs in the folding and stabilization of Gq-forming DNA sequences from the telomere and promoter gene regions by varying the salt (KCl) concentrations, mimicking the in vitro cancerous and normal cell microenvironments.

Chemical Interaction Regulates the Folding and Topology of the G-Quadruplex Exclusively Induced by a Crowder.

The folding and stability of G-quadruplexes (Gq) are correlated with cancer and depend significantly on the chemical environment. Crowders are an important constituent of living cells. However, an understanding of the folding and topology of Gq induced exclusively by a crowder is lacking.

Nucleobase Specific Understanding about the Interaction of Antimalarial Drug Chloroquine with Duplex DNA.

Antimalarial action of a drug is closely associated with the interaction with the parasite's DNA. Hence, in this study, the interaction of an important antimalarial drug, chloroquine (CLQ), has been investigated with six different sequences of DNA having pure adenine (A)-thymine (T) and pure cytosine (C)-guanine (G) as well as mixed nucleobases to achieve the nucleobase level of information in the binding of antimalarial drug with DNA along with binding induced stabilization/destabilization of DNA using different spectroscopic methods and molecular dynamics simulation technique. Further, the experiments have been also performed with 4-amino-7-chloroquinoline (7CLQ), an analogue of CLQ, to understand the role of the quinoline ring and side chain of CLQ in the binding with different sequences of DNA.

Selective Action of Antimalarial Hydroxychloroquine on the Packing of Phospholipids and Interfacial Water Associated with Lysosomal Model Membranes: A Vibrational Sum Frequency Generation Study.

Understanding the structural change of lysosomal membranes induced by hydroxychloroquine (HCQ) drug is essential as it has been considered as one of the probable mechanisms of its antimalarial action. In this context, vibrational sum frequency generation (VSFG) spectra of the O-H region of water and C-H of the hydrocarbon chain of negatively charged and zwitterionic phospholipids associated with the lysosomal membrane in the absence and presence of different concentrations of HCQ have been measured at the air/water interface. The interfacial water at the negatively charged and zwitterionic lipids gets restructured in the presence of HCQ; however, the mechanism of restructuring is different due to the charge of the head groups of lipids.

Contrasting Effect of Salts on the Binding of Antimalarial Drug Hydroxychloroquine with Different Sequences of Duplex DNA.

Hydroxychloroquine (HCQ) is an important antimalarial drug which functions plausibly by targeting the DNA of parasites. Salts play a crucial role in the functionality of various biological processes. Hence, the effect of salts (NaCl and MgCl) on the binding of HCQ with AT- and CG-DNAs as well as the binding-induced stability of both sequences of DNAs have been investigated using the spectroscopic and molecular dynamics (MD) simulation methods.

Spectroscopic and Molecular Dynamics Aspect of Antimalarial Drug Hydroxychloroquine Binding with Human Telomeric G-Quadruplex.

Hydroxychloroquine (HCQ) is an important drug that is in the trial stage for different types of cancer diseases; however, insight about the mechanism of its action is almost unknown. G-quadruplex (Gq) has been considered one of the potential targets for the cure of cancer; hence, it is essential to understand the possibility of the binding of HCQ with Gq to get a better understanding of its action. In this study, the molecular insight into the possibility of the binding of HCQ with different topological forms of Gq of the human telomere (htel) has been investigated using spectroscopic, thermochemical, and molecular dynamics simulation techniques.

DNA-Induced Reorganization of Water at Model Membrane Interfaces Investigated by Heterodyne-Detected Vibrational Sum Frequency Generation Spectroscopy.

Lipid-DNA complexes are important nonviral vectors to be used in gene therapy, which is one of the promising strategies for the cure of many diseases. Although interfacial water is expected to play a significant role in lipid-DNA complexation, a molecular-level understanding about the role of interfacial water in the DNA-lipid complexation is still sparse. In this study, the structure and orientation of water at cationic and zwitterionic lipid monolayer/water interfaces in the presence of DNA are studied by the use of interface-selective heterodyne-detected vibrational sum frequency generation (HD-VSFG) spectroscopy.

Protonation State of Dopamine Neurotransmitter at the Aqueous Interface: Vibrational Sum Frequency Generation Spectroscopy Study.

Dopamine is an important amine-based chemical neurotransmitter whose protonated state plays a crucial role in the recognition process. Understanding the structure and protonated state of dopamine at the aqueous interface is desired as the diffusion as well as binding of dopamine with the receptors take place frequently in the aqueous interface region. Vibrational sum frequency generation (VSFG) study of the OH stretch of water at the air/water interface in the presence of dopamine is performed and compared with its analog, phenylethylamine, and catechol.

The enhanced dissociation and associated surface structure of the anesthetic propofol at the water interface: vibrational sum frequency generation study.

Propofol, the most administered drug for general anesthesia, affects the acid-base equilibrium at the interfacial region of arterial blood. Hence, the structure of propofol at the water interface under different pH conditions has been measured using the surface-selective vibrational sum frequency generation (VSFG) technique to understand the hydration as well as the dissociation of propofol at the water interface. Propofol remains in its neutral form at pH ≤ 5.

The combined action of cations and anions of ionic liquids modulates the formation and stability of G-quadruplex DNA.

G-Quadruplex (Gq) formation and stabilization by any molecule is an essential requirement for its application in therapy, especially in oncology. Metal cations have shown higher propensity of the formation of the Gq structure and its stabilization. In this study, the role of both cations and anions of ionic liquids (ILs) on the Gq formation of human telomere (hTeloG) and its stability was investigated using spectroscopic and molecular dynamics simulation techniques.

Signature of the surface hydrated proton and associated restructuring of water at model membrane interfaces: a vibrational sum frequency generation study.

Hydrated proton at membrane interfaces plays an important role in the bioenergetic process of almost all organisms. Herein, the signature of the hydrated proton at membrane interfaces has been investigated by measuring the vibrational sum frequency generated (VSFG) spectra of negatively charged and zwitterionic lipids in the presence of different concentrations of acids. The addition of acids decreases the intensity of the OH stretch of the VSFG signal of water present at the negatively charged and zwitterionic lipids along with the enhanced intensity of the broad VSFG signal in the range of 2500-2800 cm-1.

Spectroscopic and Simulation Studies of the Sequence-Dependent DNA Destabilization by a Fungicide.

The understanding of the structural change of DNA induced by fungicides is essential as the non-targeted action of fungicides causes genotoxicity, leading to several serious diseases such as cancer, behavioral change, and nausea. In this study, the binding of an important fungicide, namely, -dodecylguanidine acetate (dodine), with B-DNA having different sequences of nucleobases and its effect on the structure of B-DNA has been investigated using spectroscopic and simulation methods. In general, the addition of dodine destabilizes DNA; however, the binding of dodine causing the destabilization of DNA is highly sequence dependent.

Photophysical Properties of Noncanonical Amino Acid 7-Fluorotryptophan Sharply Different from Those of Canonical Derivative Tryptophan: Spectroscopic and Quantum Chemical Calculations.

Due to the limited number of naturally existing canonical amino acids, several noncanonical amino acids have been designed to understand the diverse complex biological functions. Fluorinated amino acids are one of the important noncanonical amino acids that have been used to understand the different complex processes of proteins. In this study, the photophysical properties of the noncanonical amino acid 7-fluorotryptophan (7F-Trp) in different solvents have been investigated using extensive spectroscopic as well as quantum chemical calculation methods and compared with those of tryptophan (Trp).

Anions of Ionic Liquids Are Important Players in the Rescue of DNA Damage.

The non-targeted action of fungicides generates genotoxic effect in vertebrates by perturbing the structure of DNA, which impacts its replication and transcriptional process, leading to several serious gene associated diseases. Hence, finding a suitable medium that can reduce/reverse the structural perturbation of DNA induced by fungicide, viz. dodine, is essential.

Experimental insight into enzyme catalysis and dynamics: A review on applications of state of art spectroscopic methods.

Enzymes are dynamic in nature and understanding their activity depends on exploring their overall structural fluctuation as well as transformation at the active site in free state as well as turnover conditions. In this chapter, the application of several different spectroscopy techniques viz. single molecule spectroscopy, ultrafast spectroscopy and Raman spectroscopy in the context of enzyme dynamics and catalysis are discussed.