DNA can detect a complementary target sequence using Watson–Crick base pair formation; this sequence-based recognition has been applied to the development of sequence-sensing methods such as DNA microarrays of gene expression analyses (1) and single nucleotide polymorphism detection (2), chips for gene sequencing by hybridisation (3,4) and phylogenetic studies (5). In 1889, Richard Altmann investigated the chemical properties of nuclein. Role of Alkali Metal Ions in G-Quadruplex Nucleic Acid Structure and Stability G-quadruplexes are guanine-rich nucleic acids that fold by forming successive quartets of guanines (the G-tetrads), stabilized by intra-quartet hydrogen bonds, inter-quartet stacking, and cation coordination. Thus, analysis of DNA behaviour in ILs from the physicochemical standpoint is very useful for understanding DNA behaviour in the cell. investigated the interaction between IL cations and a DNA duplex (CGCGAATTCGCG)2 by MD simulations. Nucleic acids can also form Hoogsteen base pairs. d(GG)8 forms a left-handed Z-form helix in ILs but forms a B-form duplex in a low-salt aqueous buffer (49). In choline dhp, these long DNA duplexes have the same B-form conformation structure as that in aqueous solution. There are four heterocyclic bases in DNA: adenine (A), guanine (G), cytosine (C) and thymine (T). Section 1 surveys G-quadruplex structures and their interactions with alkali metal ions while Section 2 presents analytical methods used to study G … Systems for sensing specific DNA sequences are important in the fields of medicine and nanobiosensing (91–94). View Problem set 9_Nucleic acid structure and stability_answer key.pdf from BIOC 302 at University of British Columbia. Choline dhp stabilized the formation of Hoogsteen base pairs independent of the sequence, although the stability of Watson–Crick base-paired duplexes in choline dhp solution depended on the A–T content (48). It is a large polymeric molecule composed of monomers known as nucleotides. (Permission for use was received (48)). Nucleases B. 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To confirm the effect of choline dhp, we also measured Tm of DNA duplexes ODN7, ODN8, ODN9 and ODN10 (Table 2). 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None declared. From a biological viewpoint, DNA behaviour in ILs may also be relevant to the cellular environment in which DNA is found. Lecture 23 (11/9/20) Nucleic Acids A. investigated in more detail and found that choline ions are preferentially localized in the minor groove of the DNA duplex with A–T base pairs by MD simulations and nuclear magnetic resonance studies (69). 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In the past 20 years, certain remarkable features of ionic liquids (ILs) have made them attractive alternatives to water in various applications including electrochemistry, separation science, chemical synthesis and materials science (25–28). The behaviours of various DNA molecules in ILs detailed here should be useful for designing oligonucleotides for the development of nanomaterials and nanodevices. Figure 5 shows normalized UV melting curves at 260 nm for 30 μM pyrimidine motif triplexes. DES has no vapour pressure and has high thermal and chemical stability and accordingly is not volatile and does not boil when heated to high temperature. Sequences and schematic structures of (a) triplexes (Ts1, Ts2, Ts3 and iTs1) and (b) duplexes (Ds1, Ds2, Ds3 and iDs1). This finding suggests that the DNA was stabilized chemically by the hydrated IL medium, as has been observed for proteins (30). The … ... and as models for studying the forces governing the stability of nucleic acid secondary and tertiary structure. A snapshot of Ts1 after 20-ns MD simulations in the (a) absence or (b) presence of choline ions. Comparison of different linear-combination modeling algorithms for short-TE proton spectra. Supercoiling iii. In ODN7, ODN8, ODN9 and ODN10, the sequences are random. These nucleic acid analogues are of great interest due to their potential use of anti-viral agents, as inhibitors of gene expression at the transcriptional and translational levels, and as models for studying the forces governing the stability of nucleic acid secondary and tertiary structure… To achieve functionality of nanodevices, solvents free of the limitations of aqueous buffers are required. The free energy changes at 25°C (ΔG°25) of ODN9 and ODN10 in 4 M NaCl were −8.4 and −12.7 kcal mol−1, respectively. DNA (2′-deoxyribonucleic acid) is the molecular store of genetic information in nearly all living systems. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. DNA duplexes with the highest A–T contents showed the highest Tms in choline dhp-containing solution. In a low-salt buffer, spectroscopic data are consistent with a mixed B-/B*-form structure; however, d(A4T4)4 has a markedly different CD spectrum in DES, indicating the change in its secondary structure (49). Figure 6 shows the binding sites of choline ions around ODN1 drawn by MD trajectories (68). Thermal stability of DNA triplexes. aMelting temperature was calculated at a strand concentration of 5 μM. We thus demonstrated that choline dhp more effectively stabilized the triplex than small molecules evaluated previously (66,67). Although DNA is reasonably stable in aqueous solution, non-physiological temperature, pH and ionic strength disrupt the DNA helix and cause denaturation. bMelting temperature was calculated at a strand concentration of 100 μM. In general, sodium ions approach the phosphate groups of DNA strands to neutralize their negative charge. Base Pairing and Double-Stranded Nucleic Acid structures: Most DNA exists in the famous form of a double helix, in which two linear strands of DNA are wound around one another. It is less powerful at giving information on global properties (e.g. We studied the kinetic and thermodynamic effects of locked nucleic acid (LNA) modifications on parallel and antiparallel DNA duplexes. Promoter Methylation of LEP and LEPR before and after Bariatric Surgery: A Cross-Sectional Study. Topoisomerases 4. Due to the polyanionic nature of the nucleic acid backbone, metal ions play a crucial role in the loop stability. Filled and open circles indicate Watson–Crick and Hoogsteen base pairs, respectively. We here review current knowledge about the structures and stabilities of nucleic acids in choline dhp and DES. The choline ions bound to the minor grove and major part of the major groove in Ts1 are highlighted in (c) and (d), respectively. Nucleic Acids Structure and Stability Readings 5th Edition: 278-298, 947-971 6th Edition: 284-308, This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. Similarly, choline ions bridge the first and second strands or the first and third strands to strengthen and stabilize pyrimidine motif triplex formation. Nucleic acids can thus be ‘programmed’ to adopt predefined structures by designing their primary sequence. Given that the stabilisation of the triplex in choline dhp was enthalpically driven, choline ions may increase triplex stability through their interaction with atoms in the triplex. Nucleic acids have similar basic structures with important differences. In general, the cations bind primarily to nucleotide phosphates and stabilize the ordered DNA structures by reducing the repulsive forces between the phosphate groups (43,72). Nucleic acids with G-rich motifs form G-quartets stabilized by Hoogsteen base pairs under certain conditions (Figure 1a). We demonstrate the strong influence of a solvent on the tautomeric equilibrium INTRODUCTIO 370N 2. Shortly thereafter, Portella et al. Here, it is assumed that there is a state of equilibrium between the 2 different single-stranded (A 1, A 2) and double-stranded (A1A2) states, and that the concentrations of A 1 and A 2 are the same.. A 1 + A 2 ⇔ A 1 A 2 (1). Nuclein is the material found in the nucleus, consisting mainly of nucleic acids, protein, and phosphoric acid. The onset of this transition depends on the structure of ILs: more hydrophobic cations destabilize DNA at lower IL concentrations. It was concluded that the water state affects the G-quadruplex structure, and the water state is the function of ion species (53). Finding a medium in which DNA is soluble without loss of its structure and in which it is stable for long periods of use at above room temperature has been a bottleneck in DNA nanotechnology. DNA G‐quadruplexes are four‐stranded globular nucleic acid secondary structures formed in specific G‐rich sequences with biological significance, such as human telomeres and oncogene promoters. The success of these probes can be attributed to the ease with which their conformational change upon target binding can be coupled to a variety of signal transduction mechanisms. The anions and cations in ILs are usually molecular ions with low symmetry, a feature that disfavours packing into crystals. Pyrimidine motif triplexes are stabilized under acidic conditions because one of the two hydrogen bonds in the G*C+ Hoogsteen base pairs is formed only after protonation of N3 of cytosine (Figure 1a). Thus, DNA devices should be generally reusable for multiple cycles in ILs. The well-known structure of the DNA double helix allows this information to be copied and passed on to the next generation. This review discusses the structure and stability of nucleic acids in choline dhp and DES and describes the advantages and unique properties imparted by these solvents. Tertiary structure can be predicted from the sequence, or by comparative modeling (when the structure of a homologous sequence is known). It can be represented as a list of bases which are paired in a nucleic acid molecule. However, certain sequences form different structures in ILs than in aqueous solution. 1993 May 11;21(9):2051-6. The ability to control structure of nucleic acids by mimicking intra-cellular conditions will be useful in nanotechnology applications of nucleic acids. The study by Liu et al. PNA is chemically stable and, in contrast to natural nucleic acids and peptides, PNA is expected to remain intact in living cells since it is not a substrate for natural hydrolytic enzymes and is … PNA-nucleic acid complexes. In K+/DES, a 46-mer of the human telomeric DNA sequence (dAG3(T2AG3)7) forms higher-order G-quadruplex structures composed of two individual parallel G-quadruplexes, indicating that DES provides a favourable environment for higher-order G-quadruplex structures. MacFarlane et al. Topics will include interactions, conformations, forces and thermodynamics that govern 3D structures of biological polymers, and detailed descriptions of their structures. In the past 10 years, two types of ILs have been reported as biocompatible. also reveals the feasibility of using ILs as solvents for DNA-functionalized nanomaterials. Author information: (1)Cambridge Centre for Molecular Recognition, University Chemical Laboratories, UK. Another important concept in the nucleic acid structure is that DNA and RNA polymerases add nucleotides to the 3′ end of the previously incorporated base. Packaging ii. measured the CD spectrum of the long DNA duplex obtained from salmon testes in hydrated choline dhp (47). We studied the kinetic and thermodynamic effects of locked nucleic acid (LNA) modifications on parallel and antiparallel DNA duplexes. Our group recently showed in cultured cells and forebrain slice cultures that this compound can also down regulate expression of Tyrosine hydroxylase (Th), which encodes the rate-limiting enzyme in catecholamine … Coming to the reference book it will … Qu et al. stability of GNA. These choline ions fit well into the minor groove of the A–T base pairs. Nucleotides and nucleosides. During our … Moreover, DNA triplex formation is markedly stabilized in hydrated ILs compared with aqueous solution. Thus, the parallel four-stranded structure formed by stretches of deoxycytidines (dCs) stabilized by hemiprotonated C-C+ base pairs, proposed on the basis of NMR data [5], was confirmed by the crystal structure of d(CCCT) [6]. The distributions of choline ions around ODN1 were markedly different from those of sodium ions. Room-temperature ILs provide favourable environments for reactions because with a vapour pressure close to zero, ILs are non-volatile. It is important to know how nucleic acids form their biologically active states and how these active states are stabilized. Stability changes in nucleic acids also appeared in choline chloride solution, which is not a hydrated IL (48). The eutectic mixture melts as low as 12°C. 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