Synthesis,crystal structure,DNA binding,and DNA cleavage of a zinc complex containing N,N-bis(2-pyridylmethyl)amine

A water-soluble zinc complex, [Zn(bpea)Cl₂] (1) (bpea?=?N,N-bis(2-pyridylmethyl)ethylamine), was prepared to serve as a nuclease mimic. The complex was characterized by X-ray, infrared, and UV spectroscopy. Interactions of the complex with calf thymus-DNA (ct-DNA) have been investigated by UV absorption and fluorescence spectroscopies; the mode of ct-DNA binding for 1 has been proposed. DNA cleavage activities by 1 were performed in the absence of external agents. The influences of different complex concentrations or reaction times on DNA cleavage were studied.     

Programmable DNA Nanoflowers for Biosensing,Bioimaging, and Therapeutics

DNA nanostructures have shown excellent prospects in biomedical applications owing to their unique sequence programmability, function designability, and biocompatibility. As a type of unique DNA–inorganic hybrid nanostructures, DNA nanoflowers (DNFs) have attracted considerable attention in the past few years. Precise design of the DNA sequence enables the functions of DNFs to be customized. Specifically, DNFs exhibit high physiological stability and more diverse properties by virtue of the incorporation of inorganic materials, which in turn have been applied in an assortment of biomedical fields. In this review, the design, synthesis, and biomedical applications of programmable DNFs are discussed. First, the background of DNA-based materials and the fundamentals of DNFs are briefly introduced. In the second part, two synthetic methods of DNFs are categorized as the rolling circle amplification and salt aging method, focusing on the formation mechanism of DNFs and differences between the synthetic methods. In the third part, the biomedical applications of DNFs functional materials are summarized, including biosensing, bioimaging, and therapeutics. Finally, the challenges and future opportunities of DNFs are discussed toward more widespread applications.     

Solvating,manipulating, damaging,and repairing DNA in a computer

This work highlights four different topics in modeling of DNA: (i) the importance of water and ions together with the structure and function of DNA; the hydration structure around the ions appears to be the determining factor in the ion coordination to DNA, as demonstrated in the results of our MD simulations; (ii) how MD simulations can be used to simulate single molecule manipulation experiments as a complement to reveal the structural dynamics of the studied biomolecules; (iii) how damaged DNA can be studied in computer simulations; and (iv) how repair of damaged DNA can be studied theoretically. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

DNA在碳纳米管表面的固定、表征及损伤的电化学检测

将DNA通过PDDA [poly(dimethyldiallylammonium chloride)]固定在单壁碳纳米管(CNT)表面, 形成DNA-PDDA-CNT纳米复合体, 用AFM、UV-Vis、Raman光谱及交流阻抗对其进行了表征. 用伏安法研究了1-苯基偶氮-2-萘酚(PN)与固定在CNT表面的DNA的相互作用, 结果表明PN与DNA的作用方式为嵌入作用;并且, PN能用作电化学检测DNA化学损伤的探针分子. 本文电化学检测DNA损伤的优点在于PN的氧化还原式量电位E⁰'≈0.1 V (vs. SCE, pH 5.5), 能有效降低其它电活性物质对DNA损伤电化学检测的干扰.     

DNA浓度及序列检测的电化学传感器研究

综述近期本课题组有关DNA在化学修饰电极上的电化学行为、识别和检测方面的工作。     

Stretching,Tearing, and Dissecting Single Molecules of DNA

Optical tweezers, bendable microneedles, and scanning force microscope probes make it possible to play with individual molecules of DNA, to stretch them beyond their natural length, to unzip and pull apart their strands (see schematic diagram), and to dissect them to create new molecules in situ. Depending on the method of measurement, the mechanical force necessary to separate the strands was in the range of 10–50 pN per base pair.     

Dynamic Reconfigurable DNA Nanostructures,Networks and Materials

DNA nanotechnology relies on the structural and functional information encoded in nucleic acids. Specifically, the sequence-guided reconfiguration of nucleic acids by auxiliary triggers provides a means to develop DNA switches, machines and stimuli-responsive materials. The present Review addresses recent advances in the construction and applications of dynamic reconfigurable DNA nanostructures, networks and materials. Dynamic transformations proceeding within engineered origami frames or between origami tiles, and the triggered dynamic reconfiguration of scaled supramolecular origami structures are addressed. The use of origami frameworks to assemble dynamic chiroplasmonic optical devices and to operate switchable chemical processes are discussed. Also, the dynamic operation of DNA networks is addressed, and the design of “smart” stimuli-responsive all-DNA materials and their applications are introduced. Future perspectives and applications of dynamic reconfigurable DNA nanostructures are presented.     

Spectroscopic Study of DNA Hydrolysis,DNA Intercalative,and Electrostatic Interaction Activity Exerted by Drug Based Coordination Compounds

Our work emphasized on synthesizing and characterizing neutral mononuclear copper(II) complexes with second generation fluoroquinolone drug ciprofloxacin (CFL) and some bipyridine derivatives (Aⁿ) of type [Cu(CFL)(Aⁿ)Cl] · 2H₂O. The DNA binding free energies were evaluated by studying the effect of salt concentrations on DNA binding. DNA interactions were investigated by using DNA melting temperature studies, viscosity measurements, absorption titration, and gel electrophoresis experiments. Also superoxide dismutase (SOD)‐like activity (IC₅₀ values) and antibacterial activity of metal complexes were studied. To validate the proper mechanistic pathway for plasmid DNA cleavage, gel electrophoresis experiments were carried out in presence of radical scavenging agents. The bactericidal activity of metal complexes was evaluated in terms of colony forming unit.     

DNA Nanotechnology-based Biocomputing

With silicon-based microelectronic technology pushed to its limit,scientists hunt to exploit biomolecules to power the bio-computer as substitutes.As a typical biomolecule,DNA now has been employed as a tool to create computing systems because of its superior parallel computing ability and outstanding data storage capability.However,the key challenges in this area lie in the human intervention during the computation process and the lack of platforms for central processor.DNA nanotechnology has created hundreds of complex and hierarchical DNA nanostructures with highly controllable motions by exploiting the unparalleled self-recognition properties of DNA molecule.These DNA nanostructures can provide platforms for central processor and reduce the human intervention during the computation process,which can offer unprecedented opportunities for biocomputing.In this review,recent advances in DNA nanotechnology are briefly summarized and the newly emerging concept of biocomputing with DNA nanostructures is introduced.     

Energetics,Conformation, and Recognition of DNA Duplexes Modified by Methylated Analogues of [PtCl(dien)]+

Monodentate DNA binding of [PtCl(dien)]⁺ (dien=diethylenetriamine) complexes may considerably affect the biophysical properties of DNA and consequently downstream cellular processes as a result of a large increase in the bulkiness of the nonleaving ligand by multiple methylation (see illustration).

     

Extrachromosomal DNA in bacteria

In addition to chromosomal DNA carrying the genetic information of the cell, many bacterial cells contain smaller circular DNA factors known as plasmids or episomes. These genetic elements endow the cell with additional biochemical capabilities. The fertility factors (F and F′), the antibiotic resistance factors (R), the colicinogenic factors (Col), the hemolytic factors (Hly), and other extrachromosomal DNA systems are described. These small DNA molecules can be isolated, and are therefore particularly suitable for the investigation of DNA replication and the stable establishment of genetic material in the bacterial cell.     

DNA计算机

DNA 计算机是一种基于DNA 生化反应, 与传统计算机完全不同的新型生物计算机。本文对DNA 计算的原理、实现、发展以及实现DNA 计算机的可行性、优势与不足进行了较详尽的评述。     

酸性条件下的DNA构象变化加速DNA变性解链

调控DNA的变性解链过程是DNA扩增与检测的关键步骤。对于传统的热循环DNA扩增策略,由于变温过程中热量分布不均一以及变温速度慢等不利因素,会直接影响DNA变性解链过程,从而降低DNA检测放大的效果、延长检测的时长。因此,探索快速、高效的调控DNA变性解链的方法具有重要的研究意义。本文发展了以胞嘧啶在酸性条件下的质子化反应为基础,通过改变溶液的pH值,来诱导DNA构象在Watson-Crick（WC）碱基对与Hoogsteen（HG）碱基对之间的分子构象转换,从而实现精准、快速、高效的DNA变性解链调控目标。结果表明,相较于传统的温控方法,pH调控方法能显著提高DNA变性的速率约6倍以上。本文发现pH调控方法通过降低双链DNA的反应焓约160 kJ/mol,从而提高双链DNA变性速率和效率。该方法具有用于DNA信号放大与检测等相关应用的潜力。     

O6-Alkylguanine DNA Alkyltransferase Mediated Disassembly of a DNA Tetrahedron

Tetrahedron DNA structures were formed by the assembly of three-way junction ( TWJ ) oligonucleotides containing O⁶-2′-deoxyguanosine-alkylene-O⁶-2′-deoxyguanosine (butylene and heptylene linked) intrastrand cross-links (IaCLs) lacking a phosphodiester group between the 2′-deoxyribose residues. The DNA tetrahedra containing TWJs were shown to undergo an unhooking reaction by the human DNA repair protein O⁶-alkylguanine DNA alkyltransferase (hAGT) resulting in structure disassembly. The unhooking reaction of hAGT towards the DNA tetrahedra was observed to be moderate to virtually complete depending on the protein equivalents. DNA tetrahedron structures have been explored as drug delivery platforms that release their payload in response to triggers, such as light, chemical agents or hybridization of release strands. The dismantling of DNA tetrahedron structures by a DNA repair protein contributes to the armamentarium of approaches for drug release employing DNA nanostructures.     

Anthraquinone as a redox label for DNA: synthesis, enzymatic incorporation, and electrochemistry of anthraquinone-modified nucleosides, nucleotides, and DNA

Modified 2'-deoxynucleosides and deoxynucleoside triphosphates (dNTPs) bearing anthraquinone (AQ) attached through an acetylene or propargylcarbamoyl linker at the 5-position of pyrimidine (C) or at the 7-position of 7-deazaadenine were prepared by Sonogashira cross-coupling of halogenated dNTPs with 2-ethynylanthraquinone or 2-(2-propynylcarbamoyl)anthraquinone. Polymerase incorporations of the AQ-labeled dNTPs into DNA by primer extension with KOD XL polymerase have been successfully developed. The electrochemical properties of the AQ-labeled nucleosides, nucleotides, and DNA were studied by cyclic and square-wave voltammetry, which show a distinct reversible couple of peaks around -0.4 V that make the AQ a suitable redox label for DNA.     

Synthesis,structure, DNA binding and cleavage ability of a new copper ciprofloxacin complex

The structure of 1 consists of [Cu(HCp)(phen)(H₂O)]²⁺ (HCp is ciprofloxacin and phen is 1,10-phenanthroline), two acetates, and four free water molecules. In each cation, copper displays a distorted square pyramid, coordinated to ring 3-carboxylate and 4-oxo oxygen from HCp, two nitrogens from phen, and one water molecule. There are five water molecules in each discrete complex with one coordinated to Cu center, and the other four linked to each other by intermolecular hydrogen bonds. Two uncoordinated acetates make the compound neutral. The complex exhibits higher DNA binding compared to HCp at the same conditions by fluorescence and viscosity measurements. Combining its structure with the DNA-binding result, the binding mechanism may be explained by intercalation. Moreover, 1 shows significant cleavage of DNA in the presence of a reducing agent, such as ascorbate by gel electrophoresis using supercoiled pBR322 DNA in Tris-HCl buffer (pH 7.4). The complex also has a higher activity against Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Klebsiella pneumoniae than HCp.     

Energetics,Conformation, and Recognition of DNA Duplexes Modified by Monodentate RuII Complexes Containing Terphenyl Arenes

We studied the thermodynamic properties, conformation, and recognition of DNA duplexes site‐specifically modified by monofunctional adducts of Ru^II complexes of the type [Ru^II(η⁶‐arene)(Cl)(en)]⁺, in which arene=para‐, meta‐, or ortho‐terphenyl (complexes 1 , 2 , and 3 , respectively) and en=1,2‐diaminoethane. It has been shown (J. Med. Chem. 2008 , 51, 5310) that 1 exhibits promising cytotoxic effects in human tumor cells, whereas 2 and 3 are much less cytotoxic; concomitantly with the high cytotoxicity of 1 , its DNA binding mode involves combined intercalative and monofunctional (coordination) binding modes, whereas less cytotoxic compounds 2 and 3 bind to DNA only through a monofunctional coordination to DNA bases. An analysis of conformational distortions induced in DNA by adducts of 1 and 2 revealed more extensive and stronger distortion and concomitantly greater thermodynamic destabilization of DNA by the adducts of nonintercalating 2 . Moreover, affinity of replication protein A to the DNA duplex containing adduct of 1 was pronouncedly lower than to the adduct of 2 . On the other hand, another damaged‐DNA‐binding protein, xeroderma pigmentosum protein A, did not recognize the DNA adduct of 1 or 2 . Importantly, the adducts of 1 induced a considerably lower level of repair synthesis than the adducts of 2 , which suggests enhanced persistence of the adducts of the more potent and intercalating 1 in comparison with the adducts of the less potent and nonintercalating 2 . Also interestingly, the adducts of 1 inhibited DNA polymerization more efficiently than the adducts of 2 , and they could also be bypassed by DNA polymerases with greater difficulty. Results of the present work along with those previously published support the view that monodentate Ru^II arene complexes belong to a class of anticancer agents for which structure–pharmacological relationships might be correlated with their DNA‐binding modes.     

1,4-二氢吡啶衍生物与DNA相互作用的电化学与圆二色谱研究

用电化学和圆二色谱(CD)技术研究了5个1,4-二氢吡啶(1,4-DHP)衍生物与小牛胸腺DNA(CT-DNA)的相互作用.结果表明,1,4-DHP衍生物与CT-DNA相互作用是通过嵌入的方式进行的,相互作用的强弱与1,4-DHP衍生物的立体结构有关.1,4-DHP衍生物4-取代基空间位阻越小,嵌入到CT-DNA的程度越大.相反,空间位阻较大的1,4-DHP衍生物嵌入CT-DNA程度较小.非平面结构的1,4-DHP衍生物使CT-DNA双螺旋链结构松散程度增大.