Nucleobase Interactions Research Articles

Role of nucleobase-specific interactions in the binding and bending of DNA by human male sex determination factor SRY

Y-chromosome-encoded master transcription factor SRY functions in the embryogenesis of therian mammals to initiate male development. Through interactions of its conserved high mobility-group (HMG) box within a widened DNA minor groove, SRY and related Sox factors induce sharp bends at specific DNA target sites. Here, we present the crystal structure of the SRY HMG domain bound to a DNA site containing consensus element 5’-ATTGTT. The structure contains three complexes in the asymmetric unit; in each complex, SRY forms 10 hydrogen bonds with minor-groove base atoms in 5’-CATTGT/ACAATG-3’, shifting the recognition sequence by one base pair (italics). These nucleobase interactions involve conserved residues Arg7, Asn10, and Tyr74 on one side of intercalated Ile13 (the cantilever side chain), and Arg20, Asn32 and Ser36 on the other. Unlike the less-bent NMR structure, DNA bend angles of the distinct box-DNA complexes range from 69-84°, similar to those observed in homologous Sox domain-DNA structures. Electrophoretic studies indicate that respective substitutions of Asn32, Ser36 or Tyr74 by Ala exhibit slightly attenuated specific DNA-binding affinity and bend angles (70-73°) relative to WT (79°). By contrast, respective substitutions of Arg7, Asn10 or Arg20 by Ala markedly impaired DNA-binding affinity in association with much smaller DNA bend angles (53-65°). In a rodent cell-based model of the embryonic gonadal ridge, full-length SRY variants bearing these respective, Ala substitutions exhibited significantly decreased transcriptional activation of SRY’s principal target gene (Sox9). Together, our findings suggest that nucleobase-specific hydrogen bonds by SRY are critical for specific DNA binding, bending, and transcriptional activation.

The Some pyridyl moiety based metal complexes (viz., Mn+2, Co+2 and Zn+2) as potential anticancer agents and DNA nucleobase interaction: A DFT Approach

The Some pyridyl moiety based metal complexes (viz., Mn+2, Co+2 and Zn+2) as potential anticancer agents and DNA nucleobase interaction: A DFT Approach

Xylose- and Nucleoside-Based Polymers via Thiol-ene Polymerization toward Sugar-Derived Solid Polymer Electrolytes.

A series of copolymers have been prepared via thiol-ene polymerization of bioderived α,ω-unsaturated diene monomers with dithiols toward application as solid polymer electrolytes (SPEs) for Li+-ion conduction. Amorphous polyesters and polyethers with low Tg's (-31 to -11 °C) were first prepared from xylose-based monomers (with varying lengths of fatty acid moiety) and 2,2'-(ethylenedioxy)diethanethiol (EDT). Cross-linking by incorporation of a trifunctional monomer also produced a series of SPEs with ionic conductivities up to 2.2 × 10-5 S cm-1 at 60 °C and electrochemical stability up to 5.08 V, a significant improvement over previous xylose-derived materials. Furthermore, a series of copolymers bearing nucleoside moieties were prepared to exploit the complementary base-pairing interaction of nucleobases. Flexible, transparent, and reprocessable SPE films were thus prepared with improved ionic conductivity (up to 1.5 × 10-4 S cm-1 at 60 °C), hydrolytic degradability, and potential self-healing capabilities.

Exclusion principle between the physicochemical properties of complementary nucleobases and symmetry breaking in double-stranded DNA conformations

The information contained in DNA is encoded in a double helix formed by two antiparallel and complementary sequences of nucleotides, which are stabilized by hydrogen bonds. At physiological conditions, each nucleobase possesses three main characteristics; molecular structure, functional group, and orientation in the double helix. These properties produce steric constraints that allow only complementary interactions between nucleobase pairs to form double or triple hydrogen bonds. In this work, a mathematical model is proposed to describe the pairing interactions between nucleobases according to their physicochemical properties (structure, functional group and orientation). The results suggest that stable hydrogen bonds derived from nucleobase interactions can be represented by a set of 4 hermitian matrices and a Clifford Algebra Cl(4,0). Moreover, it is shown that the allowed interactions between pairs of nucleobases enable the formulation of an exclusion principle between the states of the observables. Finally, the mathematical representation of the hydrogen bonding between complementary nucleobases suggests a preferential orientation (chirality), which could be associated with the major groove in the double helix structure of B-DNA.

Hydrogen-Bonding Interactions from Nucleobase-Decorated Supramolecular Polymer: Synthesis, Self-Assembly and Biomedical Applications.

The fabrication of supramolecular materials for biomedical applications such as drug delivery, bioimaging, wound-dressing, adhesion materials, photodynamic/photothermal therapy, infection control (as antibacterial), etc. has grown tremendously, due to their unique properties, especially the formation of hydrogen bonding. Nevertheless, void space in the integration process, lack of feasibility in the construction of supramolecular materials of natural origin in living biological systems, potential toxicity, the need for complex synthesis protocols, and costly production process limits the actual application of nanomaterials for advanced biomedical applications. On the other hand, hydrogen bonding from nucleobases is one of the strategies that shed light on the blurred deployment of nanomaterials in medical applications, given the increasing reports of supramolecular polymers that promote advanced technologies. Herein, we review the extensive body of literature about supramolecular functional biomaterials based on nucleobase hydrogen bonding pertinent to different biomedical applications. It focuses on the fundamental understanding about the synthesis, nucleobase-decorated supramolecular architecture, and novel properties with special emphasis on the recent developments in the assembly of nanostructures via hydrogen-bonding interactions of nucleobase. Moreover, the challenges, plausible solutions, and prospects of the so-called hydrogen bonding interaction from nucleobase for the fabrication of functional biomaterials are outlined.

Creating Supramolecular Functional Materials via Nucleobase Interaction: Investigating Molecular Recognition and the Fabrication of Surface Relief Gratings

Creating Supramolecular Functional Materials via Nucleobase Interaction: Investigating Molecular Recognition and the Fabrication of Surface Relief Gratings

A highly selective and sensitive electrochemical sensor for tetracycline resistant genes detection based on the non-covalent interaction of graphene oxide and nucleobase

Antibiotic resistance genes (ARGs) are causing worldwide environmental problems, however, the traditional analytical methods and test equipment for them are time-consuming and expensive. The electrochemical sensor using the non-covalent bond between graphene oxide (GO) and single-stranded tet (ss-tet) was established for specific tetracycline resistance genes (tet, composed of ss-tet and complementary ss-tet (ss-tet') in water) detection, which preparation time was only 35 min and far less than most reported sensors based on covalent bond. As the result of the detection for tet, the developed sensor not only had the low detection limit of 50.0 pM (8.1 × 102 copies·mL−1), the short detection time within 42 min, but also had satisfactory stability, excellent reproducibility, and highly selectivity (RSD < 4.43 %). Besides, it also had acceptable accuracy comparing to the real-time quantitative polymerase chain reaction (RT-qPCR) and PCR array in tet detection. Noticeably, it also had been successfully applied to tetA detection in different water samples. In brief, the prepared non-covalent bond sensor is simple, rapid, and suitable for highly selective and sensitive detection of the ARGs in actual water.

Adsorption of DNA nucleobases on single-layer Ti3C2 MXene and graphene: vdW-corrected DFT and NEGF studies.

We investigated the interaction of DNA nucleobases [adenine (A), guanine (G), thymine (T), and cytosine (C)] with single-layer Ti3C2 MXene using Van der Waals (vdW)-corrected density functional theory and non-equilibrium Green's function methods. All calculations were benchmarked against graphene. We showed that depending on the initial vertical height of a nucleobase above the Ti3C2 surface, two interaction mechanisms are possible, namely, physisorption and chemisorption. For graphene, DNA nucleobases always physisorbed onto the graphene surface irrespective of the initial vertical height of the nucleobase above the graphene sheet. The PBE+vdW binding energies for graphene are high (0.55-0.74eV) and follow the order G > A > T > C, with adsorption heights in the range of 3.16-3.22 Å, indicating strong physisorption. For Ti3C2, the PBE+vdW binding energies are relatively weaker (0.16-0.20eV) and follow the order A > G = T > C, with adsorption heights in the range of 5.51-5.60 Å, indicating weak physisorption. The binding energies for chemisorption follow the order G > A > T > C, which is the same order for physisorption. The binding energy values (5.3-7.5eV) indicate very strong chemisorption (∼40 times larger than the physisorption binding energies). Furthermore, our band structure and electronic transport analysis showed that for physisorption, there is neither significant variation in the band structure nor modulation in the transmission function and device density of states. The relatively weak physisorption and strong chemisorption show that Ti3C2 might not be capable of identifying DNA nucleobases using the physisorption method.

Some halogenated anticancer agents, role of halide (-X) and their interaction mechanism with AT/GC base pairs: A computational study

Recently, a new class of halogen-based active anticancer agents have widely been developed which shows effective binding with AT/GC base pairs of DNA nucleobases. Usually intercalation, groove binding and covalent binding mechanisms are the most common drug-DNA binding pathways; but, the groove binding mechanism plays a crucial role in the stability of such drug-DNA complexes. As anticancer agent-DNA nucleobase interactions are very difficult to investigate by using common experimental techniques; therefore, theoretical methods may be quite helpful to analyze the proper mode of interaction for such drug-DNA systems. Past literature reveals that, quantum mechanical (QM) density functional theory (DFT) method is one of the best known tool for analyzing the different binding modes of halogenated anticancer agents with DNA nucleobases. Moreover, the halogen-bonding interaction in any biological system is fundamentally understood by investigating the mechanism of donor-acceptor complex formation between donor halogens and acceptor atoms within a receptor; such study is very competent for exploring the favoured anticancer agent-DNA interaction. In this current work, our main objective is to explore the effect of some intercalating and groove binding halogen-based anticancer agents with DNA nucleobase using computational method.

A quantum mechanical prediction of C24 fullerene as a DNA nucleobase biosensor

We aim to study the interaction of different nucleobases (adenine (A), thymine (T), guanine (G), cytosine (C) and uracil (U)) with the C24 fullerene (D6d symmetry) and to get the binding sequence of these nucleobases using dispersion (D3) corrected density functional theory (DFT). To evaluate the interaction between the nucleobases with the C24 fullerene, we have performed adsorption energy calculation, NBO analysis, Mulliken charge analysis, density of state calculation, sensing response analysis and recovery time calculation. We observed that adsorption sequence of nucleobase follows the trend as A > C > G > T > U. Due to interaction between the nucleobases and C24 fullerene charge redistribution takes place between them and induces the dipole moment. Adenine can be enisled from the other DNA nucleobase molecules, while cytosine and guanine can be sensed with the recovery time of 10−14 s in gas phase. The interaction energy increases for adenine and cytosine with solvent effect confirms their application as carrier.

Nucleobase-Interaction-Directed Biomimetic Supramolecular Self-Assembly.

ConspectusThe design and fabrication of synthetic self-assembled systems that can mimic some biological features require exquisitely sophisticated components that make use of supramolecular interactions to attain enhanced structural and functional complexity. In nature, nucleobase interactions play a key role in biological functions in living organisms, including transcription and translation processes. Inspired by nature, scientists are progressively exploring nucleobase synthons to create a diverse range of functional systems with a plethora of nanostructures by virtue of molecular-recognition-directed assembly and flexible programmability of the base-pairing interactions. To that end, nucleobase-functionalized molecules and macromolecules are attracting great attention because of their versatile structures with smart and adaptive material properties such as stimuli responsiveness, interaction with external agents, and ability to repair structural defects. In this regard, a range of nucleobase-interaction-mediated hierarchical self-assembled systems have been developed to obtain biomimetic materials with unique properties. For example, a new “grafting to” strategy utilizing complementary nucleobase interactions has been demonstrated to temporarily control the functional group display on micellar surfaces. In a different approach, complementary nucleobase interactions have been explored to enable morphological transitions in functionalized diblock copolymer assembly. It has been demonstrated that complementary nucleobase interactions can drive the morphological transformation to produce highly anisotropic nanoparticles by controlling the assembly processes at multiple length scales. Furthermore, nucleobase-functionalized bottle brush polymers have been employed to generate stimuli-responsive hierarchical assembly. Finally, such interactions have been exploited to induce biomimetic segregation in polymer self-assembly, which has been employed as a template to synthesize polymers with narrow polydispersity. It is evident from these examples that the optimal design of molecular building blocks and precise positioning of the nucleobase functionality are essential for fabrication of complex supramolecular assemblies. While a considerable amount of research remains to be explored, our studies have demonstrated the potential of nucleobase-interaction-mediated supramolecular assembly to be a promising field of research enabling the development of biomimetic materials.This Account summarizes recent examples that employ nucleobase interactions to generate functional biomaterials by judicious design of the building blocks. We begin by discussing the molecular recognition properties of different nucleobases, followed by different strategies to employ nucleobase interactions in polymeric systems in order to achieve self-assembled nanomaterials with versatile properties. Moreover, some of their prospective biological/material applications such as enhanced drug encapsulation, superior adhesion, and fast self-healing properties facilitated by complementary nucleobase interactions are emphasized. Finally, we identify issues and challenges that are faced by this class of materials and propose future directions for the exploration of functional materials with the aim of promoting the development of nucleobase-functionalized systems to design the next generation of biomaterials.

Nucleobase-crosslinked poly(2-oxazoline) nanoparticles as paclitaxel carriers with enhanced stability and ultra-high drug loading capacity for breast cancer therapy

Poly(2-oxazoline) (POx) has been regarded as a potential candidate for drug delivery carrier to meet the challenges of nanomedicine clinical translation, due to its excellent biocompatibility and self-assembly properties. The drug loading capacity and stability of amphiphilic POxs as drug nanocarriers, however, tend to be insufficient. Herein, we report a strategy to prepare nucleobase-crosslinked POx nanoparticles (NPs) with enhanced stability and ultra-high paclitaxel (PTX) loading capacity for breast cancer therapy. An amphiphilic amine-functionalized POx (PMBEOx-NH2) was firstly prepared through a click reaction between cysteamines and vinyl groups in poly(2-methyl-2-oxazoline)-block-poly (2‑butyl‑2-oxazoline-co-2-butenyl-2-oxazoline) (PMBEOx). Complementary nucleobase-pairs adenine (A) and uracil (U) were subsequently conjugated to PMBEOx-NH2 to give functional POxs (POxA and POxU), respectively. Due to the nucleobase interactions formed between A and U, NPs formed by POxA and POxU at a molar ratio of 1:1 displayed ultrahigh PTX loading capacity (38.2%, PTX/POxA@U), excellent stability, and reduced particle size compared to the uncross-linked PTX-loaded NPs (PTX/PMBEOx). Besides the prolonged blood circulation and enhanced tumor accumulation, the smaller PTX/POxA@U NPs also have better tumor penetration ability compared with PTX/PMBEOx, thus leading to a higher tumor suppression rate in two murine breast cancer models (E0711 and 4T1). These results proved that the therapeutic effect of chemotherapeutic drugs could be improved remarkably through a reasonable optimization of nanocarriers.

DNA Nucleobase Interaction with Silicon Carbide Nanosheet

DNA Nucleobase Interaction with Silicon Carbide Nanosheet

Complementary Nucleobase Interactions Drive Co-Assembly of Drugs and Nanocarriers for Selective Cancer Chemotherapy.

A new concept in cooperative adenine–uracil (A–U) hydrogen bonding interactions between anticancer drugs and nanocarrier complexes was successfully demonstrated by invoking the co-assembly of water soluble, uracil end-capped polyethylene glycol polymer (BU-PEG) upon association with the hydrophobic drug adenine-modified rhodamine (A-R6G). This concept holds promise as a smart and versatile drug delivery system for the achievement of targeted, more efficient cancer chemotherapy. Due to A–U base pairing between BU-PEG and A-R6G, BU-PEG has high tendency to interact with A-R6G, which leads to the formation of self-assembled A-R6G/BU-PEG nanogels in aqueous solution. The resulting nanogels exhibit a number of unique physical properties, including extremely high A-R6G-loading capacity, well-controlled, pH-triggered A-R6G release behavior, and excellent structural stability in biological media. Importantly, a series of in vitro cellular experiments clearly demonstrated that A-R6G/BU-PEG nanogels improved the selective uptake of A-R6G by cancer cells via endocytosis and promoted the intracellular release of A-R6G to subsequently induce apoptotic cell death, while control rhodamine/BU-PEG nanogels did not exert selective toxicity in cancer or normal cell lines. Overall, these results indicate that cooperative A–U base pairing within nanogels is a critical factor that improves selective drug uptake and effectively promotes apoptotic programmed cell death in cancer cells.

Reconfigurable Two‐Dimensional DNA Lattices: Static and Dynamic Angle Control

AbstractBranched DNA motifs serve as the basic construction elements for all synthetic DNA nanostructures. However, precise control of branching orientation remains a key challenge to further heighten the overall structural order. In this study, we use two strategies to control the branching orientation. The first one is based on immobile Holliday junctions which employ specific nucleotide sequences at the branch points which dictate their orientation. The second strategy is to use angle‐enforcing struts to fix the branching orientation with flexible spacers at the branch points. We have also demonstrated that the branching orientation control can be achieved dynamically, either by canonical Watson–Crick base pairing or non‐canonical nucleobase interactions (e.g., i‐motif and G‐quadruplex). With precise angle control and feedback from the chemical environment, these results will enable novel DNA nanomechanical sensing devices, and precisely‐ordered three‐dimensional architectures.

Reconfigurable Two-Dimensional DNA Lattices: Static and Dynamic Angle Control.

Branched DNA motifs serve as the basic construction elements for all synthetic DNA nanostructures. However, precise control of branching orientation remains a key challenge to further heighten the overall structural order. In this study, we use two strategies to control the branching orientation. The first one is based on immobile Holliday junctions which employ specific nucleotide sequences at the branch points which dictate their orientation. The second strategy is to use angle-enforcing struts to fix the branching orientation with flexible spacers at the branch points. We have also demonstrated that the branching orientation control can be achieved dynamically, either by canonical Watson-Crick base pairing or non-canonical nucleobase interactions (e.g., i-motif and G-quadruplex). With precise angle control and feedback from the chemical environment, these results will enable novel DNA nanomechanical sensing devices, and precisely-ordered three-dimensional architectures.

Indium nitride nanotube interaction with different DNA nucleobases: Quantum chemical analysis

DNA sequencing gives us an ideal opportunity to promote the well-being by helping personal or precision medicine. Here, we inspected the interaction of DNA nucleobases with the InNNT by using DFT computations in order to find a DNA sequencer. We found that the nucleobases prefer to be adsorbed perpendicularly on the InNNT rather than horizontally. The energy released upon the DNA nucleobases adsorption on the InNNT shows the order of guanine (G, 1.62 eV) > thymine (T, 1.49) > cytosine (C, 1.45) > adenine (A, 0.82). Based on our analysis of energy decomposition, the mainly the nature of perpendicular and horizontal interaction is covalent and π-π interaction, respectively. The nucleobase interaction may meaningfully increase the electrical conductivity of the InNNT, so the sensing response of InNNT to G, T, C, and A nucleobases was anticipated to be 289, 100, 91, and 13 respectively. Based on the results, there is a possibility of using InNNT for sensing the difference among G, T, C, and A nucleobases selectively, being helpful to determine the nucleobase sequence in DNA.

DNA nucleobase interaction driven electronic and optical fingerprints in gallium selenide monolayer for DNA sequencing devices

The interaction of DNA nucleobases with monolayer GaSe has been studied with in DFT framework using vdW functional. We found that nucleobases are physisorbed on the GaSe monolayer. The order of binding energy per atom is C > T > G > A. The room temperature recovery time estimated to be maximum of 113.88 µs for T + GaSe indicting reusability of the GaSe based devices. The modulation in the electronic structures of GaSe has been clearly captured within the simulated STM measurements. We also demonstrate quantum capacitance as a key parameter for sensing applications. Furthermore, in optical properties, electron energy loss (EEL) spectra show red shift in photon energy on nucleobase adsorption in UV region. The red shift is maximum of 0.92 eV for E⊥c and 0.50 eV for E||c. In nutshell, GaSe monolayer exhibit anisotropic optical response in UV-region which can be highly beneficial for developing polarized optical sensors. Our results demonstrate that GaSe monolayer can be utilized to fabricate reusable DNA sequencing devices for biotechnology and medical science.

Double-helical assembly of heterodimeric nanoclusters into supercrystals.

DNA has long been used as a template for the construction of helical assemblies of inorganic nanoparticles1-5. For example, gold nanoparticles decorated with DNA (or with peptides) can create helical assemblies6-9. But without such biological ligands, helices are difficult to achieve and their mechanism of formation is challenging to understand10,11. Atomically precise nanoclusters that are protected by ligands such as thiolate12,13 have demonstrated hierarchical structural complexity in their assembly at the interparticle and intraparticle levels, similar to biomolecules and their assemblies14. Furthermore, carrier dynamics can be controlled by engineering the structure of the nanoclusters15. But these nanoclusters usually have isotropic structures16,17 and often assemble into commonly found supercrystals18. Here we report the synthesis of homodimeric and heterodimeric gold nanoclusters and their self-assembly into superstructures. While thehomodimeric nanoclusters form layer-by-layer superstructures, the heterodimeric nanoclusters self-assemble into double- and quadruple-helical superstructures. These complex arrangements are the result of two different motif pairs, one pair per monomer, where each motif bonds with its paired motif on a neighbouring heterodimer. This motif pairing is reminiscent of the paired interactions of nucleobases in DNA helices. Meanwhile, the surrounding ligands on the clusters show doubly or triply paired steric interactions. The helical assembly is driven by van der Waals interactions through particle rotation and conformational matching. Furthermore, the heterodimeric clusters have a carrier lifetime that is roughly 65 times longer than that of the homodimeric clusters. Our findings suggest new approaches for increasing complexity in the structural design and engineering of precision in supercrystals.

The interaction of nucleobases with an AlN nanotube for electronic DNA sequencing

Deoxyribonucleic acid (DNA) sequencing provides the opportunity to advance prosperity by helping individuals or developing precision medications. The potential application of a zigzag (10, 0) AlN nanotube (AlNNT) as a DNA sequencer is studied herein by using B3LYP-gCP-D3 density functional model chemistry. The energy released after adsorption of DNA nucleobases by the AlNNT lies in the following order: guanine (G, 1.22 eV) > cytosine (C, 1.12) ≈ thymine (T, 1.09) ≫ adenine (A, 0.71). Energy decomposition analysis reveals that the nucleobases that include an oxygen atom (G, C, and T) interact covalently with the AlNNT while the A base adsorbs via a π–π stacking interaction. The adsorption of DNA nucleobases on the AlNNT clearly increases its electrical conductivity, and the sensing response of the AlNNT toward G, C, T, or A is predicted to be 1339, 608, 523, or 248. Thus, an AlNNT could be applied to selectively sense G, C, T, and A, which is conducive to determining the nucleobase sequence of DNA. Short recovery times are also obtained for desorption of the DNA nucleobases.