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1.
Top Curr Chem (Cham) ; 378(1): 13, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31925680

RESUMO

The use of magnetic nanoparticles (MNPs), such as iron oxide nanoparticles (IONPs), in biomedicine is considered to be a valuable alternative to the more traditional materials due to their chemical stability, cost-effectiveness, surface functionalization, and the possibility to selectively attach and transport targeted species to the desired location under a magnetic field. One of the many main applications of MNPs is DNA separation, which enables genetic material manipulation; consequently, MNPs are used in numerous biotechnological methods, such as gene transfection and molecular recognition systems. In addition, the interaction between the surfaces of MNPs and DNA molecules and the magnetic nature of the resulting composite have facilitated the development of safe and effective gene delivery vectors to treat significant diseases, such as cancer and neurological disorders. Furthermore, the special recognition properties of nucleic acids based on the binding capacity of DNA and the magnetic behavior of the nanoparticles allowing magnetic separation and concentration of analytes have led to the development of biosensors and diagnostic assays; however, both of these applications face important challenges in terms of the improvement of selective nanocarriers and biosensing capacity. In this review, we discuss some aspects of the properties and surface functionalization of MNPs, the interactions between DNA and IONPs, the preparation of DNA nanoplatforms and their biotechnological applications, such as the magnetic separation of DNA, magnetofection, preparation of DNA vaccines, and molecular recognition tools.


Assuntos
DNA/química , Compostos Férricos/química , Nanopartículas de Magnetita/química , Nanomedicina , DNA/isolamento & purificação , Portadores de Fármacos/química , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Vacinas de DNA/química , Vacinas de DNA/imunologia
2.
Biophys Chem ; 256: 106270, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31706136

RESUMO

DNA strands can be designed to assemble into stable three-dimensional structures, based on Watson-Crick base pairing rules. The simplest of these is the DNA tetrahedron that is composed of four oligonucleotides. We have re-designed the sequence of a DNA tetrahedron so that it contains a single (AATT) binding site for the minor groove binding ligand Hoechst 33258. We examined the stability of this structure by placing fluorescent groups within each of its edges and have shown that all the edges melt at the same temperature in the absence of the ligand. The minor groove ligand still binds to its recognition sequence within the tetrahedron and increases the melting temperature of the folded complex. This ligand-induced stabilisation is propagated into the adjacent helical arms and the tetrahedron melts as a single entity in a cooperative fashion.


Assuntos
DNA/química , Ligantes , Sequência de Bases , Sítios de Ligação , Bisbenzimidazol/química , Bisbenzimidazol/metabolismo , Conformação de Ácido Nucleico , Transição de Fase/efeitos da radiação , Espectrometria de Fluorescência , Temperatura de Transição , Raios Ultravioleta
3.
Phys Rev Lett ; 123(22): 228101, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31868408

RESUMO

Understanding the spatial organization of the genome in the cell nucleus is one of the current grand challenges in biophysics. Certain biochemical-or epigenetic-marks that are deposited along the genome are thought to play an important, yet poorly understood, role in determining genome organization and cell identity. The physical principles underlying the interplay between epigenetic dynamics and genome folding remain elusive. Here we propose and study a theory that assumes a coupling between epigenetic mark and genome densities, and which can be applied at the scale of the whole nucleus. We show that equilibrium models are not compatible with experiments and a qualitative agreement is recovered by accounting for nonequilibrium processes that can stabilize microphase separated epigenomic domains. We finally discuss the potential biophysical origin of these terms.


Assuntos
Núcleo Celular/genética , Modelos Genéticos , Biofísica , Núcleo Celular/química , DNA/química , DNA/genética , DNA/metabolismo , Metilação de DNA , Genoma , Histonas/química , Histonas/genética , Histonas/metabolismo
4.
J Chem Phys ; 151(23): 230902, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864250

RESUMO

Polymeric materials are ubiquitous in our daily lives, and they play a significant role in many technological applications. The general predictive framework for the behavior of soft polymeric materials can be divided into two vastly different approaches. Highly coarse-grained models capture polymers as flexible random walks, resulting in general predictions of physical behavior but lack chemical specificity. Detailed atomistic models contain molecular detail but are frequently computationally intractable for exhaustive materials discovery. In this perspective, we discuss theoretical models that successfully bridge these disparate approaches. We identify intermediate-scale physical models that are amenable to theoretical analyses while containing sufficient granular detail to capture a range of molecular-level processes. We then provide several problems in materials engineering and biological physics where multiscale physics is essential in their behavior.


Assuntos
DNA/química , Polímeros/química , Humanos , Modelos Moleculares
5.
Biomed Khim ; 65(6): 477-484, 2019 Oct.
Artigo em Russo | MEDLINE | ID: mdl-31876518

RESUMO

Using random (combinatorial) DNA-libraries with various degrees of diversity, it was shown that their amplification by polymerase chain reaction in real time resulted in appearance of a maximum on amplification curves. The relative decrease of fluorescence after passing the maximum was directly proportional to the logarithm of the number of oligonucleotide sequence variants in the random DNA-library provided that this number was within in the interval from 1 to 104 and remained practically unaltered when the number of variants was in the interval from 105 to 108. The obtained dependence was used in the course of SELEX to evaluate changes in the diversity of random DNA-libraries from round to round in selection of DNA-aptamers to the recombinant SMAD4 protein. As a result, oligonucleotides containing sequences able to form a site of SMAD4-DNA interactions known as SBE (SMAD-binding element) have been selected thus indicating that the SMAD4-SBE interaction dominates the aptamer selection.


Assuntos
Aptâmeros de Nucleotídeos/química , DNA/química , Biblioteca Gênica , Técnica de Seleção de Aptâmeros , Reação em Cadeia da Polimerase
6.
Chem Soc Rev ; 48(23): 5564-5595, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31670726

RESUMO

The design and applications of some inorganic two-dimensional (2D) nanomaterials such as graphene, graphyne, and borophene have been widely studied in recent years. Meanwhile, it has been noticed that self-assembling two-dimensional organic biomaterials (2DOBMs) including films, membranes, nanosheets, nanoribbons, grids, arrays, and lattices based on various biomolecules also exhibited promising structures, functions, and applications. The in-depth studies on the self-assembly formation, structural and functional tailoring of 2DOBMs open new avenues for the next generation of novel nanomaterials with adjustable structure and functions, which would further promote the applications of 2DOBMs in materials science, nanodevices, energy and environmental science, biomedicine, tissue engineering, and analytical science. In this review, we summarize important information on the basic principles to fabricate self-assembling 2DOBMs based on peptides, proteins, DNA, RNA, viruses, and other biopolymers. The potential strategies and techniques for tailoring and controlling the structures and functions of 2DOBMs are presented and discussed further. The function-specific biomedical applications of 2DOBMs in biosensors, biomimetic mineralization, cell growth, drug/gene delivery, and bioimaging are also highlighted.


Assuntos
Materiais Biocompatíveis/química , Animais , Técnicas Biossensoriais/métodos , DNA/química , Portadores de Fármacos/química , Nanoestruturas/química , Imagem Óptica , Polímeros/química , Proteínas/química , Engenharia Tecidual
7.
Chem Commun (Camb) ; 55(93): 14039-14042, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690924

RESUMO

In this work, we have proposed a new strategy to expand the function of a protein. By taking a protease as an example, it can be engineered to make up the shortcoming of natural proteases, and thus it can efficiently and selectively hydrolyze a desired protein even in a complex biological fluid.


Assuntos
Inibidores Enzimáticos/química , Nanoconjugados/química , Peptídeo Hidrolases/química , Aptâmeros de Nucleotídeos/química , DNA/química , Ouro/química , Nanopartículas Metálicas/química , Biologia Molecular/métodos , RNA/química
8.
Adv Exp Med Biol ; 1174: 331-370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31713205

RESUMO

DNA nanotechnology has revolutionised the capabilities to shape and control three-dimensional structures at the nanometre scale. Designer sensors, nanopores and ion-channels built from DNA have great potential for both cross-disciplinary research and applications. Here, we introduce the concept of structural DNA nanotechnology, including DNA origami, and give an overview of the work flow from design to assembly, characterisation and application of DNA-based functional systems. Chemical functionalisation of DNA has opened up pathways to transform static DNA structures into dynamic nanomechanical sensors. We further introduce nanopore sensing as a powerful label-free single-molecule technique and discuss how it can benefit from DNA nanotechnology. Especially exciting is the possibility to create membrane-inserted DNA nanochannels that mimic their protein-based natural counterparts in form and function. In this chapter we review the status quo of DNA sensors, nanopores and ion channels, highlighting opportunities and challenges for their future development.


Assuntos
Técnicas Biossensoriais , DNA , Nanoporos , Nanotecnologia , Técnicas Biossensoriais/tendências , DNA/química , Canais Iônicos/química , Nanotecnologia/tendências
10.
Chem Commun (Camb) ; 55(93): 14074-14077, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31696869

RESUMO

We discovered that the function of cytochrome C can be modulated by DNA nanoribbons. Meanwhile, the interplay between the DNA nanoribbons and the native cytochrome C and the possible mechanisms are also discussed.


Assuntos
Citocromos c/metabolismo , DNA/metabolismo , Nanoestruturas/química , Peroxidases/metabolismo , Animais , Catálise , Citocromos c/química , DNA/química , Guaiacol/química , Cavalos , Oxirredução , Peroxidases/química , Ligação Proteica
11.
J Chem Phys ; 151(16): 164902, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31675856

RESUMO

Most of the anticancer drugs bind to double-stranded DNA (dsDNA) by intercalative-binding mode. Although experimental studies have become available recently, a molecular-level understanding of the interactions between the drug and dsDNA that lead to the stability of the intercalated drug is lacking. Of particular interest are the modifications of the mechanical properties of dsDNA observed in experiments. The latter could affect many biological functions, such as DNA transcription and replication. Here, we probe, via all-atom molecular dynamics (MD) simulations, the change in the mechanical properties of intercalated drug-DNA complexes for two intercalators, daunomycin and ethidium. We find that, upon drug intercalation, the stretch modulus of DNA increases significantly, whereas its persistence length and bending modulus decrease. Steered MD simulations reveal that it requires higher forces to stretch the intercalated dsDNA complexes than the normal dsDNA. Adopting various pulling protocols to study force-induced DNA melting, we find that the dissociation of dsDNA becomes difficult in the presence of intercalators. The results obtained here provide a plausible mechanism of function of the anticancer drugs, i.e., via altering the mechanical properties of DNA. We also discuss long-time consequences of using these drugs, which require further in vivo investigations.


Assuntos
Antineoplásicos/química , DNA/química , Substâncias Intercalantes/química , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico
12.
Chem Commun (Camb) ; 55(92): 13932-13935, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31686058

RESUMO

In this work, a bipedal DNA walker was employed to mediate an efficient enzyme-free exponential isothermal DNA signal amplification. On the basis of the bipedal DNA walker mediated enzyme-free exponential isothermal signal amplification, an electrochemiluminescence (ECL) biosensor was constructed for sensitive and rapid detection of microRNA (miRNA) with a limit of detection down to 0.24 fM and requiring less than 40 min.


Assuntos
Técnicas Biossensoriais/métodos , DNA/química , MicroRNAs/análise , Linhagem Celular Tumoral , Complexos de Coordenação/química , DNA/metabolismo , Humanos , Limite de Detecção , Medições Luminescentes , Nanopartículas Metálicas/química , Hibridização de Ácido Nucleico , Rutênio/química , Titânio/química
13.
Phys Chem Chem Phys ; 21(42): 23514-23520, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31617554

RESUMO

Inherent molecular fluctuations are known to have a significant influence on the charge transport properties of biomolecules like DNA, PNA and proteins. In this work, we show ways to control these fluctuations and further demonstrate their use to enhance the conductance of two widely studied molecular wires, namely dsDNA (DNA) and G4 Quadruplex (G4-Quad). We quantify the molecular fluctuation in terms of the root mean square deviation (RMSD) of the molecule. In the case of DNA, we use temperature to control the fluctuations, while in the case of G4-Quad the fluctuations are tuned by the ions inside the pore. The electronic coupling between the bases of dsDNA and G4-Quad, which measures the conductance of these molecular wires, shows a non-monotonic behaviour with the increase in fluctuation. We find values of fluctuation which give rise to maximum electronic coupling and hence high conductivity for both the cases. In the case of DNA, these optimal fluctuations (∼2.5 Å) are achieved at a temperature of 210 K, which gives rise to an electronic coupling of 0.135 eV between the DNA bases. The optimal fluctuations in G4-Quad are achieved (∼7 Å) in a 4 base pair long system with 2 Na+ ions inside the pore, giving rise to an electronic coupling of 0.09 eV.


Assuntos
DNA/química , Condutividade Elétrica , Quadruplex G , Simulação de Dinâmica Molecular , Ácidos Nucleicos Peptídicos/química , Proteínas/química , Teoria Quântica , Temperatura Ambiente
14.
Phys Chem Chem Phys ; 21(41): 22869-22878, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31599901

RESUMO

The non-biological 2'-deoxy-2'-fluoro-arabinonucleic acid (2'F-ANA) may be used as a valid alternative to DNA in biomedical and electronic applications because of its higher resistance to hydrolysis and nuclease degradation. However, the advantage of using 2'F-ANA in such applications also depends on its charge-transfer properties compared to DNA. In this study, we compare the charge conduction properties of model 2'F-ANA and DNA double-strands, using structural snapshots from MD simulations to calculate the electronic couplings and reorganization energies associated with the hole transfer steps between adjacent nucleobase pairs. Inserting these charge-transfer parameters into a kinetic model for charge conduction, we find similar conductive properties for DNA and 2'F-ANA. Moreover, we find that 2'F-ANA's enhanced chemical stability does not correspond to a reduction in the nucleobase π-stack structural flexibility relevant to both electronic couplings and reorganization free energies. Our results promote the use of 2'F-ANA in applications that can be based on charge transport, such as biosensing and chip technology, where its chemical stability and conductivity can advantageously combine.


Assuntos
Arabinonucleotídeos/química , Biotecnologia/métodos , DNA/química , Eletrônica , Simulação de Dinâmica Molecular
15.
Chem Commun (Camb) ; 55(86): 12980-12983, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31603440

RESUMO

Nuclear factor kappa B p50 (NF-κB p50) induces various biological processes. In this study, a highly selective and sensitive electrochemiluminescence (ECL) biosensor for the detection of NF-κB p50 has been developed, which combines the high selectivity of the proximity hybridization assay (PHA) with the high efficiency of the hybridization chain reaction (HCR).


Assuntos
Técnicas Biossensoriais/métodos , Subunidade p50 de NF-kappa B/análise , DNA/química , Técnicas Eletroquímicas , Eletrodos , Humanos , Medições Luminescentes , Técnicas de Amplificação de Ácido Nucleico , Hibridização de Ácido Nucleico
16.
Phys Chem Chem Phys ; 21(41): 22782-22793, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31595896

RESUMO

The theoretical assignment of electronic spectra of polyatomic molecules is a challenging problem that requires the specification of the character of a large number of electronic states. We propose a procedure for automatically determining the character of electronic transitions and apply it to the study of UV spectra of DNA bases in the gas phase and in the aqueous environment. The procedure is based on the computation of electronic wave function overlaps and accounts for an extensive sampling of nuclear geometries. Novelties of this work are the theoretical assignment of the electronic spectra of DNA bases up to 190 nm and a state specific analysis of solvation effects. By accounting for different effects contributing to the total solvent shift we obtained a good agreement between the computed and experimental spectra. Effects of vibrational averaging, temperature and solvent-induced structural changes shift excitation energies to lower values. Solvent-solute electrostatic interactions are state specific and strongly destabilize nRyd states, and to lesser extent nπ* and πRyd states. Altogether, this results in the stabilization of ππ* states and destabilization of nπ*, πRyd and nRyd states in solution.


Assuntos
Técnicas de Química Analítica/métodos , DNA/química , Solventes/química , Análise Espectral , Gases/química , Eletricidade Estática , Raios Ultravioleta
17.
J Phys Chem Lett ; 10(21): 6750-6754, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31609626

RESUMO

Photodynamic therapy is a promising approach to treat a variety of superficial tumors and other diseases. One of its major limitations arises from its dependence on molecular oxygen, which decreases the efficiency of the therapy in hypoxia conditions commonly developed by solid tumors. The present contribution reveals the molecular mechanism of a modified thymine bearing a nitroimidazole substituent, a photosensitizer able to produce highly harmful interstrand cross-links in the DNA double strand after irradiation selectively in absence of oxygen. The mechanism is resolved at a fully atomistic and electronic level relying on quantum mechanics (CASPT2, coupled-cluster, DFT, and TD-DFT methods), classical molecular dynamics, and advanced biased QM/MM simulations, revealing an energy penalty of ∼8 kcal/mol for the anionic nitromidazole release. Our findings indicate that the global interstrand cross-link production is driven by a combination of multiple factors, namely, the reverse energy penalty, the diffusion of the nitroimidazole anion, and the further reactivity of the formed thymine radical. On the basis of these results, we also suggest some possible strategies to improve the efficiency of interstrand cross-link production.


Assuntos
DNA/química , Nitroimidazóis/química , DNA/metabolismo , Ligações de Hidrogênio , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico , Fármacos Fotossensibilizantes/química , Teoria Quântica
18.
Anal Bioanal Chem ; 411(27): 7221-7231, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31583449

RESUMO

DNA methylation is a typical epigenetic phenomenon. Numerous methods for detecting global DNA methylation levels have been developed, among which LC-MS/MS has emerged as an excellent method from the viewpoint of sensitivity, reproducibility, and cost. However, LC-MS/MS methods have limitations due to a lack of the stability and the standardization required for a laboratory assay. The present study aimed to establish a robust assay that guarantees highly accurate measurements of global DNA methylation levels. There are at least three facets of the developed method. The first is discovery of the solvent conditions to minimize sodium adducts. The second is improvement of separation of nucleosides by LC using the columns that had not been used in previous similar studies. The third is success in reduction of the uncertainty of the measurement results, which was achieved by the calibration using the ratio of mdC but not the absolute amount in the presence of internal standards. These facets represent the advantage over methods reported previously. Our developed method enables quantification of DNA methylation with a short time length (8 min) for one analysis as well as with the high reproducibility of measurements that is represented by the inter-day CV% being less than 5%. In addition, data obtained from measuring global DNA methylation levels in cultured cell lines, with or without pharmacological demethylation, support its use for biomedical research. This assay is expected to allow us to conduct initial screening of epigenetic alterations or aberration in a variety of cells.


Assuntos
Metilação de DNA , DNA/química , Espectrometria de Massas em Tandem/métodos , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão/economia , Cromatografia Líquida de Alta Pressão/métodos , Citidina/análogos & derivados , Citidina/análise , Citidina/genética , DNA/genética , Humanos , Espectrometria de Massas em Tandem/economia , Fatores de Tempo
19.
J Chem Phys ; 151(12): 125101, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31575173

RESUMO

Gene regulation is one of the most important fundamental biological processes in living cells. It involves multiple protein molecules that locate specific sites on DNA and assemble gene initiation or gene repression multimolecular complexes. While the protein search dynamics for DNA targets has been intensively investigated, the role of intermolecular interactions during the genetic activation or repression remains not well quantified. Here, we present a simple one-dimensional model of target search for two interacting molecules that can reversibly form a dimer molecular complex, which also participates in the search process. In addition, the proteins have finite residence times on specific target sites, and the gene is activated or repressed when both proteins are simultaneously present at the target. The model is analyzed using first-passage analytical calculations and Monte Carlo computer simulations. It is shown that the search dynamics exhibit a complex behavior depending on the strength of intermolecular interactions and on the target residence times. We also found that the search time shows a nonmonotonic behavior as a function of the dissociation rate for the molecular complex. Physical-chemical arguments to explain these observations are presented. Our theoretical approach highlights the importance of molecular interactions in the complex process of gene activation/repression by multiple transcription factor proteins.


Assuntos
DNA/química , Modelos Químicos , Simulação por Computador , DNA/genética , DNA/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Cinética , Método de Monte Carlo , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
20.
J Chem Phys ; 151(12): 125102, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31575191

RESUMO

We present an analytical model for the role of hydrogen bonding on the spin-orbit coupling of a model DNA molecule. Here, we analyze in detail the electric fields due to the polarization of the hydrogen bond on the DNA base pairs and derive, within a tight binding analytical band folding approach, an intrinsic Rashba coupling which should dictate the order of the spin active effects in the chiral-induced spin selectivity effect. The coupling found is ten times larger than the intrinsic coupling estimated previously and points out to the predominant role of hydrogen bonding in addition to chirality in the case of biological molecules. We expect similar dominant effects in oligopeptides, where the chiral structure is supported by hydrogen-bonding and bears on orbital carrying transport electrons.


Assuntos
DNA/química , Modelos Químicos , Transporte de Elétrons , Ligações de Hidrogênio , Oligopeptídeos/química
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