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Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
In parallel, the conformational probing was simplified by the introduction of the fluorescent methods. In order to probe the dynamics of both the wild-type operator and the aptamer RNAs, the fluorescent nucleotide 2′-deoxy-2-aminopurine was incorporated at key adenosine positions (Parrott et al. 2000). This appeared in fact as a sensitive probe for the conformational changes. The recognition by coat protein was enhanced, unaffected, or decreased, depending on the site of substitution, consistent with the known protein-RNA contacts seen in crystal structures of the complexes. It was concluded that the detailed conformational dynamics of aptamers and wild-type RNA ligands for the same protein target were remarkably similar. The fluorescent technique was used to measure kinetics of the complex I formation between the MS2 coat dimer and members of three distinct RNA aptamer families which were known to bind to the same site on the protein (Lago et al. 2001). Remarkably, the complex I consisted of a single-coat dimer and one RNA molecule. The authors concluded that the conformational changes in the protein ligand during formation of the complex I might play a role in the triggering of the capsid self-assembly.
Mutagenic Consequences Of Chemical Reaction with DNA
Published in Philip L. Grover, Chemical Carcinogens and DNA, 2019
In contrast to 5-bromouracil, low concentrations of 2 aminopurine and 2,6-diami-nopurine are mutagenic to bacteria. The likeliest implication is that mispairings by these bases are for some reason not recognized as mismatches in E. coli, possibly because they are ambiguous. 2-Aminopurine mutagenesis, however, does appear subject to correction by the 3ℓ to 5ℓ exonuclease activity of bacteriophage T4 polymerase.146
Interferons and their Mechanisms of Action
Published in Velibor Krsmanović, James F. Whitfield, Malignant Cell Secretion, 2019
The induction of IFN-β mRNA synthesis occurs even in the presence of an inhibitor of protein synthesis. This suggests that the IFN-β gene is activated by preexisting factors which are modified in response to the inducing signal. This activation is likely to occur, at least in part, through the phosphorylation of some of these factors. It has, indeed, been demonstrated that 2-aminopurine (2-AP) is able to block specifically the induction of the IFN-β gene by dsRNA and viruses.135 Since 2-AP is a potent inhibitor of both the heme dependent and the dsRNA dependent protein kinase,136 it is thus tempting to postulate that the later kinase is actually the receptor of dsRNA in the cytoplasm. This hypothesis which has been proposed previously by Marcus24 correlates well with the known characteristics of the IFN induction process. In particular, this hypothesis would also explain the phenomenon of priming. Indeed, in the cells which are sensitive to priming, this dsRNA-dependent protein kinase may, in fact, be lacking or expressed at a low level. Pretreatment of the cells with IFN could restore its expression, since the enzyme is IFN-inducible.
Advances in the discovery of novel agents for the treatment of glaucoma
Published in Expert Opinion on Drug Discovery, 2021
Francesco Mincione, Alessio Nocentini, Claudiu T. Supuran
INO-8875 (compound 72), a highly selective adenosine A1 receptor agonist, is the N-cyclopentyl6-aminopurine riboside incorporating a nitrate ester functionality at the 5-hydroxymethyl moiety of the sugar (Figure 16) and was initially developed as a cardiovascular drug [115]. INO-8875 was shown to induce a strong blockade of atrioventricular (A-V)-nodal conduction, with few cardiovascular side effects when administered systemically, but its topical administration directly into the eye led to a strong IOP lowering [116], probably due to the agonism of the adenosine receptors and the release of NO, which, as shown above is by itself one of the mechanisms inducing this effect [116]. INO-8875 is presently in Phase II clinical trials as an antiglaucoma agent [116].
A label-free technique for accurate detection of nucleic acid–based self-avoiding molecular recognition systems supplemented multiple cross-displacement amplification and nanoparticles based biosensor
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Yi Wang, Yan Wang, Hong Wang, Jianguo Xu, Changyun Ye
In this report, we introduce a “self-avoiding molecular recognition system” (SAMRS) as a class of DNA analogues employed to support MCDA assay [4,5]. With the MCDA primers containing SAMRS components, no undesired results were obtained in blank controls and negative controls, and only a positive signal was seen in positive control (Figure 4). In SAMRS–MCDA assay, the SAMRS components, including A* (2-aminopurine), T* (2-thiotymine), C* (N4-ethylcytosine) and G* (hypoxanthine), are used for replacing the natural A, T, C and G nucleobases at some sites (near the 3′-end of primers) of MCDA primers (Table 2) [4]. SAMRS T* pairs with natural A; SAMRS A* pairs with natural T; SAMRS G* pairs with natural C and SAMRS C* pairs with natural G. However, SAMRS A*: SAMRS T* and SAMRS C*: SAMRS G* base pairs cannot contribute the stability of the helix due to they either form 1 or 1.5 bonds [5,16,17]. The special pairing rules indicate that SAMRS components cannot interact with other SAMRS components (even when these molecules exhibit 100% complementarity), thus MCDA primers containing SAMRS molecules bind solely to their intended natural complements (target sequence) and prevent primer-dimers in SAMRS–MCDA assay. Accordingly, SAMRS–MCDA method successfully removes the false-positive results, arising from self-amplification (false-positive results generated from interactions between or within primers) and non-specific amplification (false-positive results generated from non-target hybrids) (Figure 4).
The use of a 2-aminopurine-containing split G-quadruplex for sequence-specific DNA detection
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Sung Hyun Hwang, Woo Young Kwon, Hyunmin Eun, Sehan Jeong, Jun Seok Park, Kwang Jin Kim, Hyung Joo Kim, Sang Hyun Lee, Kyungmoon Park, Jeong-Jun Yoon, Yung-Hun Yang, Ki Soo Park
Fluorescent nucleobase analogues not only retain the chemical and biological properties of natural nucleobases, such as base pairing and enzyme binding, but they also possess conformation-dependent fluorescence efficiencies [4–6]. A representative example of this type of nucleobase is 2-aminopurine (2-AP), which displays efficient fluorescence emission when incorporated in a single-stranded DNA [7,8]. Moreover, the fluorescence of 2-AP is strongly quenched when present in double-stranded DNA as a consequence of its adenine-like Watson–Crick base pairing with thymine. This unique fluorescence property of 2-AP has been exploited in the design of systems that detect target analytes such as nucleic acids, metal ions and enzyme activities [9–11]. However, the wide spread use of this strategy is limited by the fact that the signal enhancement displayed by 2-AP in nucleic acid-based sensors is often low owing to the existence of stacking interactions with surrounding nucleobases in a single-stranded state, which causes emission quenching.