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Chembiochem : a European Journal of... May 2021Synthetic efforts towards nucleosides, nucleotides, oligonucleotides and nucleic acids covalently mercurated at one or more of their base moieties are summarized,... (Review)
Review
Synthetic efforts towards nucleosides, nucleotides, oligonucleotides and nucleic acids covalently mercurated at one or more of their base moieties are summarized, followed by a discussion of the proposed, realized and abandoned applications of this unique class of compounds. Special emphasis is given to fields in which active research is ongoing, notably the use of Hg -mediated base pairing to improve the hybridization properties of oligonucleotide probes. Finally, this minireview attempts to anticipate potential future applications of organomercury nucleic acids.
Topics: Animals; Base Pairing; Coordination Complexes; Genotyping Techniques; Humans; Mercury; Nucleic Acids; Oligonucleotides; Polymorphism, Single Nucleotide
PubMed: 33410571
DOI: 10.1002/cbic.202000821 -
Nucleic Acids Research Oct 2020The N4-methylation of cytidine (m4C and m42C) in RNA plays important roles in both bacterial and eukaryotic cells. In this work, we synthesized a series of m4C and m42C...
The N4-methylation of cytidine (m4C and m42C) in RNA plays important roles in both bacterial and eukaryotic cells. In this work, we synthesized a series of m4C and m42C modified RNA oligonucleotides, conducted their base pairing and bioactivity studies, and solved three new crystal structures of the RNA duplexes containing these two modifications. Our thermostability and X-ray crystallography studies, together with the molecular dynamic simulation studies, demonstrated that m4C retains a regular C:G base pairing pattern in RNA duplex and has a relatively small effect on its base pairing stability and specificity. By contrast, the m42C modification disrupts the C:G pair and significantly decreases the duplex stability through a conformational shift of native Watson-Crick pair to a wobble-like pattern with the formation of two hydrogen bonds. This double-methylated m42C also results in the loss of base pairing discrimination between C:G and other mismatched pairs like C:A, C:T and C:C. The biochemical investigation of these two modified residues in the reverse transcription model shows that both mono- or di-methylated cytosine bases could specify the C:T pair and induce the G to T mutation using HIV-1 RT. In the presence of other reverse transcriptases with higher fidelity like AMV-RT, the methylation could either retain the normal nucleotide incorporation or completely inhibit the DNA synthesis. These results indicate the methylation at N4-position of cytidine is a molecular mechanism to fine tune base pairing specificity and affect the coding efficiency and fidelity during gene replication.
Topics: Base Pairing; Cytidine; Methylation; Oligoribonucleotides; RNA; RNA Folding
PubMed: 32941619
DOI: 10.1093/nar/gkaa737 -
Molecules (Basel, Switzerland) Oct 2019Nucleic acids and proteins are two major classes of biopolymers in living systems. Whereas nucleic acids are characterized by robust molecular recognition properties,... (Review)
Review
Nucleic acids and proteins are two major classes of biopolymers in living systems. Whereas nucleic acids are characterized by robust molecular recognition properties, essential for the reliable storage and transmission of the genetic information, the variability of structures displayed by proteins and their adaptability to the environment make them ideal functional materials. One of the major goals of DNA nanotechnology-and indeed its initial motivation-is to bridge these two worlds in a rational fashion. Combining the predictable base-pairing rule of DNA with chemical conjugation strategies and modern protein engineering methods has enabled the realization of complex DNA-protein architectures with programmable structural features and intriguing functionalities. In this review, we will focus on a special class of biohybrid structures, characterized by one or many enzyme molecules linked to a DNA scaffold with nanometer-scale precision. After an initial survey of the most important methods for coupling DNA oligomers to proteins, we will report the strategies adopted until now for organizing these conjugates in a predictable spatial arrangement. The major focus of this review will be on the consequences of such manipulations on the binding and kinetic properties of single enzymes and enzyme complexes: an interesting aspect of artificial DNA-enzyme hybrids, often reported in the literature, however, not yet entirely understood and whose full comprehension may open the way to new opportunities in protein science.
Topics: Base Pairing; DNA; Enzymes; Nanostructures; Nanotechnology; Nucleic Acid Conformation; Proteins
PubMed: 31615123
DOI: 10.3390/molecules24203694 -
Viruses May 2023Base pairing based on hydrogen bonding has, since its inception, been crucial in the antiviral activity of arabinosyladenine, 2'-deoxyuridines (i.e., IDU, TFT, BVDU),...
Base pairing based on hydrogen bonding has, since its inception, been crucial in the antiviral activity of arabinosyladenine, 2'-deoxyuridines (i.e., IDU, TFT, BVDU), acyclic nucleoside analogues (i.e., acyclovir) and nucleoside reverse transcriptase inhibitors (NRTIs). Base pairing based on hydrogen bonding also plays a key role in the mechanism of action of various acyclic nucleoside phosphonates (ANPs) such as adefovir, tenofovir, cidofovir and O-DAPYs, thus explaining their activity against a wide array of DNA viruses (human hepatitis B virus (HBV), human immunodeficiency (HIV) and human herpes viruses (i.e., human cytomegalovirus)). Hydrogen bonding (base pairing) also seems to be involved in the inhibitory activity of Cf1743 (and its prodrug FV-100) against varicella-zoster virus (VZV) and in the activity of sofosbuvir against hepatitis C virus and that of remdesivir against SARS-CoV-2 (COVID-19). Hydrogen bonding (base pairing) may also explain the broad-spectrum antiviral effects of ribavirin and favipiravir. This may lead to lethal mutagenesis (error catastrophe), as has been demonstrated with molnutegravir in its activity against SARS-CoV-2.
Topics: Humans; Antiviral Agents; Nucleosides; Base Pairing; Hydrogen Bonding; COVID-19; SARS-CoV-2; Viruses
PubMed: 37243232
DOI: 10.3390/v15051145 -
Metallomics : Integrated Biometal... Apr 2021Artificial metal base pairs have become increasingly important in nucleic acids chemistry due to their high thermal stability, water solubility, orthogonality to natural... (Review)
Review
Artificial metal base pairs have become increasingly important in nucleic acids chemistry due to their high thermal stability, water solubility, orthogonality to natural base pairs, and low cost of production. These interesting properties combined with ease of chemical and enzymatic synthesis have prompted their use in several practical applications, including the construction of nanomolecular devices, ions sensors, and metal nanowires. Chemical synthesis of metal base pairs is highly efficient and enables the rapid screening of novel metal base pair candidates. However, chemical synthesis is limited to rather short oligonucleotides and requires rather important synthetic efforts. Herein, we discuss recent progress made for the enzymatic construction of metal base pairs that can alleviate some of these limitations. First, we highlight the possibility of generating metal base pairs using canonical nucleotides and then describe how modified nucleotides can be used in this context. We also provide a description of the main analytical techniques used for the analysis of the nature and the formation of metal base pairs together with relevant examples of their applications.
Topics: Base Pairing; Coordination Complexes; DNA-Directed DNA Polymerase; Metals; Nucleic Acids
PubMed: 33791776
DOI: 10.1093/mtomcs/mfab016 -
Nucleic Acids Research Apr 2022Unnatural base pairs (UBPs) which exhibit a selectivity against pairing with canonical nucleobases provide a powerful tool for the development of nucleic acid-based...
Unnatural base pairs (UBPs) which exhibit a selectivity against pairing with canonical nucleobases provide a powerful tool for the development of nucleic acid-based technologies. As an alternative strategy to the conventional UBP designs, which involve utility of different recognition modes at the Watson-Crick interface, we now report that the exclusive base pairing can be achieved through the spatial separation of recognition units. The design concept was demonstrated with the alkynylated purine (NPu, OPu) and pyridazine (NPz, OPz) nucleosides endowed with nucleobase-like 2-aminopyrimidine or 2-pyridone ('pseudo-nucleobases') on their major groove side. These alkynylated purines and pyridazines exhibited exclusive and stable pairing properties by the formation of complementary hydrogen bonds between the pseudo-nucleobases in the DNA major groove as revealed by comprehensive Tm measurements, 2D-NMR analyses, and MD simulations. Moreover, the alkynylated purine-pyridazine pairs enabled dramatic stabilization of the DNA duplex upon consecutive incorporation while maintaining a high sequence-specificity. The present study showcases the separation of the recognition interface as a promising strategy for developing new types of UBPs.
Topics: Base Pairing; DNA; Hydrogen Bonding; Nucleic Acid Conformation; Nucleic Acids; Nucleosides
PubMed: 35234916
DOI: 10.1093/nar/gkac140 -
Current Opinion in Chemical Biology Oct 2016DNA and RNA are remarkable because they can both encode information and possess desired properties, including the ability to bind specific targets or catalyze specific... (Review)
Review
DNA and RNA are remarkable because they can both encode information and possess desired properties, including the ability to bind specific targets or catalyze specific reactions. Nucleotide modifications that do not interfere with enzymatic synthesis are now being used to bestow DNA or RNA with properties that further increase their utility, including phosphate and sugar modifications that increase nuclease resistance, nucleobase modifications that increase the range of activities possible, and even whole nucleobase replacement that results in selective pairing and the creation of unnatural base pairs that increase the information content. These modifications are increasingly being applied both in vitro and in vivo, including in efforts to create semi-synthetic organisms with altered or expanded genetic alphabets.
Topics: Base Pairing; Catalysis; DNA; Hydrophobic and Hydrophilic Interactions; Proteins; RNA; SELEX Aptamer Technique
PubMed: 27565457
DOI: 10.1016/j.cbpa.2016.08.001 -
European Biophysics Journal : EBJ Jul 2020Despite the common acceptance that the enthalpy of DNA duplex unfolding does not depend on temperature and is greater for the CG base pair held by three hydrogen bonds...
Despite the common acceptance that the enthalpy of DNA duplex unfolding does not depend on temperature and is greater for the CG base pair held by three hydrogen bonds than for the AT base pair held by only two, direct calorimetric measurements have shown that the enthalpic and entropic contributions of both base pairs are temperature dependent and at all temperatures are greater for the AT than the CG pair. The temperature dependence results from hydration of the apolar surfaces of bases that become exposed upon duplex dissociation. The larger enthalpic and entropic contributions of the AT pair are caused by water fixed by this pair in the minor groove of DNA and released on duplex dissociation. Analysis of the experimental thermodynamic characteristics of unfolding/refolding DNA duplexes of various compositions shows that the enthalpy of base pairing is negligibly small, while the entropic contribution is considerable. Thus, DNA base pairing is entropy driven and is coupled to the enthalpy driven van der Waals base pair stacking. Each of these two processes is responsible for about half the Gibbs energy of duplex stabilization, but all the enthalpy, i.e., the total heat of melting, results from dissociation of the stacked base pairs. Both these processes tightly cooperate: while the pairing of conjugate bases is critical for recognition of complementary strands, stacking of the flat apolar surfaces of the base pairs reinforces the DNA duplex formed.
Topics: Base Pairing; Biomechanical Phenomena; DNA; Mechanical Phenomena; Surface Properties; Thermodynamics; Water
PubMed: 32462263
DOI: 10.1007/s00249-020-01437-w -
Metal Ions in Life Sciences 2012Base-pairing in the naturally occurring DNA and RNA oligonucleotide duplexes is based on π-stacking, hydrogen bonding, and shape complementarity between the nucleobases... (Review)
Review
Base-pairing in the naturally occurring DNA and RNA oligonucleotide duplexes is based on π-stacking, hydrogen bonding, and shape complementarity between the nucleobases adenine, thymine, guanine, and cytosine as well as on the hydrophobic-hydrophilic balance in aqueous media. This complex system of multiple supramolecular interactions is the product of a long-term evolutionary process and thus highly optimized to serve its biological functions such as information storage and processing. After the successful implementation of automated DNA synthesis, chemists have begun to introduce artificial modifications inside the core of the DNA double helix in order to study various aspects of base pairing, generate new base pairs orthogonal to the natural ones, and equip the biopolymer with entirely new functions. The idea to replace the hydrogen bonding interactions with metal coordination between ligand-like nucleosides and suitable transition metal ions culminated in the development of a plethora of artificial base-pairing systems termed "metal base-pairs" which were shown to strongly enhance the DNA duplex stability. Furthermore, they show great potential for the use of DNA as a molecular wire in nanoscale electronic architectures. Although single electrons have proven to be transmitted by natural DNA over a distance of several base pairs, the high ohmic resistance of unmodified oligonucleotides was identified as a serious obstacle. By exchanging some or all of the Watson-Crick base pairs in DNA with metal complexes, this problem may be solved. In the future, these research efforts are supposed to lead to DNA-like materials with superior conductivity for nano-electronic applications. Other fields of potential application such as DNA-based supramolecular architecture and catalysis may be strongly influenced by these developments as well. This text is meant to illustrate the basic concepts of metal-base pairing and give an outline over recent developments in this field.
Topics: Base Pairing; Coordination Complexes; DNA; Metals; Molecular Structure; Nucleic Acid Conformation
PubMed: 22210343
DOI: 10.1007/978-94-007-2172-2_10 -
Chemical & Pharmaceutical Bulletin 2018In this review, we have summarized the research effort into the development of unnatural base pairs beyond standard Watson-Crick (WC) base pairs for synthetic biology.... (Review)
Review
In this review, we have summarized the research effort into the development of unnatural base pairs beyond standard Watson-Crick (WC) base pairs for synthetic biology. Prior to introducing our research results, we present investigations by four outstanding groups in the field. Their research results demonstrate the importance of shape complementarity and stacking ability as well as hydrogen-bonding (H-bonding) patterns for unnatural base pairs. On the basis of this research background, we developed unnatural base pairs consisting of imidazo[5',4':4.5]pyrido[2,3-d]pyrimidines and 1,8-naphthyridines, i.e., Im : Na pairs. Since Im bases are recognized as ring-expanded purines and Na bases are recognized as ring-expanded pyrimidines, Im : Na pairs are expected to satisfy the criteria of shape complementarity and enhanced stacking ability. In addition, these pairs have four non-canonical H-bonds. Because of these preferable properties, ImN : NaO, one of the Im : Na pairs, is recognized as a complementary base pair in not only single nucleotide insertion, but also the PCR.
Topics: Base Pairing; Hydrogen Bonding; Naphthyridines; Physical Phenomena; Purines; Pyrimidines; Synthetic Biology
PubMed: 29386463
DOI: 10.1248/cpb.c17-00685