Category: 452-06-2

Wang, Kai-Bo; Dickerhoff, Jonathan; Wu, Guanhui; Yang, Danzhou published the artcile< PDGFR-β Promoter Forms a Vacancy G-Quadruplex that Can Be Filled in by dGMP: Solution Structure and Molecular Recognition of Guanine Metabolites and Drugs>, Safety of 7H-Purin-2-amine, the main research area is vacancy G quadruplex PDGFRbeta promoter dGMP conformation guanine drug.

Aberrant expression of PDGFR-β is associated with a number of diseases. The G-quadruplexes (G4s) formed in PDGFR-β gene promoter are transcriptional modulators and amenable to small mol. targeting. The major G4 formed in the PDGFR-β gene promoter was previously shown to have a broken G-strand. Herein, we report that the PDGFR-β gene promoter sequence forms a vacancy G-quadruplex (vG4) which can be filled in and stabilized by physiol. relevant guanine metabolites, such as dGMP, GMP, and cGMP, as well as guanine-derivative drugs. We determined the NMR structure of the dGMP-fill-in PDGFR-β vG4 in K+ solution This is the first structure of a guanine-metabolite-fill-in vG4 based on a human gene promoter sequence. Our structure and systematic anal. elucidate the contributions of Hoogsten hydrogen bonds, sugar, and phosphate moieties to the specific G-vacancy fill-in. Intriguingly, an equilibrium of 3′- and 5′-end vG4s is present in the PDGFR-β promoter sequence, and dGMP favors the 5′-end fill-in. Guanine metabolites and drugs were tested and showed a conserved selectivity for the 5′-vacancy, except for cGMP. CGMP binds both the 3′- and 5′-end vG4s and forms two fill-in G4s with similar population. Significantly, guanine metabolites are involved in many physiol. and pathol. processes in human cells; thus, our results provide a structural basis to understand their potential regulatory functions by interaction with promoter vG4s. Moreover, the NMR structure can guide rational design of ligands that target the PDGFR-β vG4.

Journal of the American Chemical Society published new progress about Drugs. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Safety of 7H-Purin-2-amine.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Tang, Ke; Roca, Jorjethe; Chen, Rong; Ansari, Anjum; Liang, Jie published the artcile< Thermodynamics of unfolding mechanisms of mouse mammary tumor virus pseudoknot from a coarse-grained loop-entropy model>, Category: imidazoles-derivatives, the main research area is mammary tumor virus pseudoknot thermodn entropy model; Energy landscape; Fluorescence spectroscopy; Heat capacity; Loop entropy; PK3D; Pseudoknotted RNA; RNA folding; RNA hairpin; Unfolding mechanism.

Pseudoknotted RNA mols. play important biol. roles that depend on their folded structure. To understand the underlying principles that determine their thermodn. and folding/unfolding mechanisms, we carried out a study on a variant of the mouse mammary tumor virus pseudoknotted RNA (VPK), a widely studied model system for RNA pseudoknots. Our method is based on a coarse-grained discrete-state model and the algorithm of PK3D (pseudoknot structure predictor in three-dimensional space), with RNA loops explicitly constructed and their conformational entropic effects incorporated. Our loop entropy calculations are validated by accurately capturing previously measured melting temperatures of RNA hairpins with varying loop lengths. For each of the hairpins that constitutes the VPK, we identified alternative conformations that are more stable than the hairpin structures at low temperatures and predicted their populations at different temperatures Our predictions were validated by thermodn. experiments on these hairpins. We further computed the heat capacity profiles of VPK, which are in excellent agreement with available exptl. data. Notably, our model provides detailed information on the unfolding mechanisms of pseudoknotted RNA. Anal. of the distribution of base-pairing probability of VPK reveals a cooperative unfolding mechanism instead of a simple sequential unfolding of first one stem and then the other. Specifically, we find a simultaneous “”loosening”” of both stems as the temperature is raised, whereby both stems become partially melted and co-exist during the unfolding process.

Journal of Biological Physics published new progress about Algorithm. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Category: imidazoles-derivatives.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ilgu, Muslum; Yan, Shuting; Khounlo, Ryan M.; Lamm, Monica H.; Nilsen-Hamilton, Marit published the artcile< Common secondary and tertiary structural features of aptamer-ligand interaction shared by RNA aptamers with different primary sequences>, COA of Formula: C5H5N5, the main research area is secondary tertiary structural feature RNA aptamer ligand interaction; 2-aminopurine (2AP), molecular dynamics; aminoglycoside; isothermal titration calorimetry; neomycin-B RNA aptamer.

Aptamer selection can yield many oligonucleotides with different sequences and affinities for the target mol. Here, we have combined computational and exptl. approaches to understand if aptamers with different sequences but the same mol. target share structural and dynamical features. NEO1A, with a known NMR-solved structure, displays a flexible loop that interacts differently with individual aminoglycosides, its ligand affinities and specificities are responsive to ionic strength, and it possesses an adenosine in the loop that is critical for high-affinity ligand binding. NEO2A was obtained from the same selection and, although they are only 43% identical in overall sequence, NEO1A and NEO2A share similar loop sequences. Exptl. anal. by 1D NMR and 2-aminopurine reporters combined with mol. dynamics modeling revealed similar structural and dynamical characteristics in both aptamers. These results are consistent with the hypothesis that the target ligand drives aptamer structure and also selects relevant dynamical characteristics for high-affinity aptamer-ligand interaction. Furthermore, they suggest that it might be possible to “”migrate”” structural and dynamical features between aptamer group members with different primary sequences but with the same target ligand.

Molecules published new progress about Affinity. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, COA of Formula: C5H5N5.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Snyder, Joshua A.; Charnay, Aaron P.; Kohl, Forrest R.; Zhang, Yuyuan; Kohler, Bern published the artcile< DNA-like photophysics in self-assembled silver(I)-nucleobase nanofibers>, Recommanded Product: 7H-Purin-2-amine, the main research area is silver nucleobase self assembly nanofiber transient absorption.

Supramol. assemblies form when silver nitrate is added to an aqueous solution of adenine (Ade) or 2-aminopurine (2AP) in a 2:1 mol ratio. Atomic force microscopy images reveal nanofibers that are ∼30 nm in diameter and micrometers in length in the dried film formed from a room-temperature solution Femtosecond broadband transient absorption spectroscopy was used to investigate the dynamics of excited states formed by UV excitation of the nanofibers in room-temperature aqueous solutions in an effort to learn how nonradiative decay pathways of the uncomplexed nucleobases are altered in the silver-ion-mediated assemblies. The changes in the spectroscopy and dynamics of Ade and 2AP upon forming nanofibers with silver ions closely parallel the ones seen when these bases are organized into DNA strands. The similarities strongly suggest that these structures feature extensive π-π stacking interactions between nucleobases. The results show that time-resolved spectroscopy combined with growing understanding of the photophysics of DNA strands can deliver new insights into the properties of metal-nucleobase nanoassemblies.

Journal of Physical Chemistry B published new progress about Luminescence. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Recommanded Product: 7H-Purin-2-amine.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Wamsley, Max; Nawalage, Samadhi; Hu, Juan; Collier, Willard E.; Zhang, Dongmao published the artcile< Back to the Drawing Board: A Unifying First-Principle Model for Correlating Sample UV-Vis Absorption and Fluorescence Emission>, Computed Properties of 452-06-2, the main research area is anthracene fluorescence emission first principle method.

The popular textbook and literature model I(λx,λm) = or its variants for correlating the sample absorption and fluorescence often fails even for the simplest samples where the fluorophore is the only light absorber. Reported is a first-principle model I(λx,λm) = for correlating the sample fluorescence measured with a conventional spectrofluorometer and its UV-vis absorbance quantified with a conventional UV-vis spectrophotometer. This model can be simplified or expanded for a variety of fluorescence analyses. First, it enables curve-fitting fluorescence intensity as a function of the fluorophore or sample absorbance over a sample concentration range impossible with existing models. Second, it provides the theor. foundation for an inner-filter-effect (IFE)-correction method developed earlier and explains math. the linearity between the IFE-corrected fluorescence and the fluorophore concentration or absorbance. Third, this model can be expanded for quant. mechanistic studies of fluorescence intensity variations triggered by stimuli treatments. One demonstrated example is to quantify temperature effects on the emission-wavelength-specific and total fluorescence quantum yield of anthracene. We expect that this first-principle model will be broadly adopted for both student education that promotes evidence-based learning and a variety of fluorescence applications where disentangling sample absorption and emission are critical for reliable data anal.

Analytical Chemistry (Washington, DC, United States) published new progress about Fluorescence. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Computed Properties of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Xu, Xiaochen; Egger, Michaela; Chen, Hao; Bartosik, Karolina; Micura, Ronald published the artcile< Insights into xanthine riboswitch structure and metal ion-mediated ligand recognition>, Related Products of 452-06-2, the main research area is xanthine riboswitch NMT1 metal ion mediated ligand recognition.

Riboswitches are conserved functional domains in mRNA that mostly exist in bacteria. They regulate gene expression in response to varying concentrations of metabolites or metal ions. Recently, the NMT1 RNA motif has been identified to selectively bind xanthine and uric acid, resp., both are involved in the metabolic pathway of purine degradation Here, we report a crystal structure of this RNA bound to xanthine. Overall, the riboswitch exhibits a rod-like, continuously stacked fold composed of three stems and two internal junctions. The binding-pocket is determined by the highly conserved junctional sequence J1 between stem P1 and P2a, and engages a long-distance Watson-Crick base pair to junction J2. Xanthine inserts between a G-U pair from the major groove side and is sandwiched between base triples. Strikingly, a Mg2+ ion is inner-sphere coordinated to O6 of xanthine and a non-bridging oxygen of a backbone phosphate. Two further hydrated Mg2+ ions participate in extensive interactions between xanthine and the pocket. Our structure model is verified by ligand binding anal. to selected riboswitch mutants using isothermal titration calorimetry, and by fluorescence spectroscopic anal. of RNA folding using 2-aminopurine-modified variants. Together, our study highlights the principles of metal ion-mediated ligand recognition by the xanthine riboswitch.

Nucleic Acids Research published new progress about Crystal structure. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Related Products of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Brovarets, Ol′ha O.; Hovorun, Dmytro M. published the artcile< Key microstructural mechanisms of the 2-aminopurine mutagenicity: Results of extensive quantum-chemical research>, HPLC of Formula: 452-06-2, the main research area is review quantum 2aminopurine mutagenicity tautomerization; 2-Aminopurine; H-bond: hydrogen bond; Watson–Crick↔wobble mutagenic tautomerization; induced mutation; quantum-chemical calculation; transition; transversion.

A review. As of today, a great amount of exptl. and theor. phenomenol. data have been collected in the literature according the mutagenic action of the classical mutagen – 2-aminopurine (2AP). However, so far they have not received proper explanation and substantiation. In this Opinion Piece, we provide an overview of recent progress in computational design and modeling of the physico-chem. mechanisms of the mutagenic action of 2AP. Results of quantum-chem. studies, aimed at the elucidation of the key microstructural mechanisms of the mutagenicity of 2AP, have been summarized here. In this context, for the first time it was outlined the most important surveys: Why 2AP is incorporated into DNA in trace concentrations? Whether classical mechanisms presented in the literature according the formation of the rare tautomers of canonical DNA bases work also for base analog – 2AP? In what way 2AP induces replication and incorporation errors? Whether the amino-imino tautomerisation of 2AP is related to its mutagenicity, that is whether the 2AP* rare tautomer is mutagenic? It is emphasized that the applied approach has a proper theor. substantiation, since it is based on our microstructural theory of the spontaneous point mutagenesis in DNA, and at the same time it accumulates scenarios of the origin of the induced point errors – transitions and transversions, which the classical Watson-Crick tautomeric hypothesis permits. Moreover, using author′s methodol., the profiles of the main physico-chem. characteristics for the tautomerisation reactions involving 2AP, which are integral parts of the biol. important tautomerically-conformational transformations, have been presented. Obtained results open new perspectives for prediction and design of the mutagenic derivatives of the nucleotide bases of any structure and origin before their synthesis and also for planning of new experiments and interpretation of the existing data. Abbreviations2AP2-AminopurineAadenineCcytosineDPTdouble proton transferGguanineIRCintrinsic reaction coordinateKPkey pointTthyminewwobbleWCWatson-CrickvdWvan der WaalsH-bondhydrogen bondCommunicated by Ramaswamy H. Sarma

Journal of Biomolecular Structure and Dynamics published new progress about DNA Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, HPLC of Formula: 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

He, Yanping; Zhou, Yibo; Chen, Da; Liu, Juewen published the artcile< Global Folding of a Na+-Specific DNAzyme Studied by FRET>, Name: 7H-Purin-2-amine, the main research area is DNAzymes; FRET; aptamers; protein folding; sodium.

Recently, a few RNA-cleaving DNAzymes have been isolated with excellent specificity for Na+, and some of them contain a Na+-binding aptamer. This metal recognition mechanism is different from that of most previously reported DNAzymes. When using 2-aminopurine (2AP) as a probe, interesting local folding induced by Na+ was recently observed In this work, FRET was used to probe the global folding of the Ce13d DNAzyme; one of the Na+-specific DNAzymes. FRET pairs were at different locations, which yielded a total of five constructs to probe the three-way junction structure with a large loop. With endlabeled DNAzymes, the global structure appears to be quite rigid with little folding upon adding up to 200 mM monovalent metal ions, although some minor differences were observed between Li+, Na+, and K+. This lack of significant conformational change is also consistent with CD spectroscopy data. The loop was then labeled with an internal tetramethylrhodamine fluorophore at the G14 position, and its cleavage activity was partially retained. A clear Na+-dependent folding was observed with spectral crossover. From a biosensing standpoint, global folding based sensors are unlikely to work due to the overall rigid structure of the DNAzyme. Therefore, the best way to use this DNAzyme to discriminate Na+ from K+ is based on cleavage activity, followed by probing local folding, whereas global folding is the least effective for metal discrimination.

ChemBioChem published new progress about 452-06-2. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Name: 7H-Purin-2-amine.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Wickhorst, Peter Jonas; Ihmels, Heiko; Paululat, Thomas published the artcile< Studies on the Interactions of 3,11-Difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium and Insulin with the Quadruplex-Forming Oligonucleotide Sequence a2 from the Insulin-Linked Polymorphic Region>, Quality Control of 452-06-2, the main research area is interaction quadruplex oligonucleotide sequence insulin linked polymorphic region; DNA recognition; ILPR; spectroscopic methods.

Recently, several quadruplex-DNA-forming sequences have been identified in the insulin-linked polymorphic region (ILPR), which is a guanine-rich oligonucleotide sequence in the promoter region of insulin. The formation of this non-canonical quadruplex DNA (G4-DNA) has been shown to be involved in the biol. activity of the ILPR, specifically with regard to its interplay with insulin. In this context, this contribution reports on the investigation of the association of the quadruplex-forming ILPR sequence a2 with insulin as well as with the well-known G4-DNA ligand 3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium (1), also named RHPS4, by optical and NMR spectroscopy. CD- and NMR-spectroscopic measurements confirmed the preferential formation of an antiparallel quadruplex structure of a2 with four stacked guanine quartets. Furthermore, ligand 1 has high affinity toward a2 and binds by terminal π stacking to the G1-G11-G15-G25 quartet. In addition, the spectroscopic studies pointed to an association of insulin to the deoxyribose backbone of the loops of a2.

Molecules published new progress about Absorption. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Quality Control of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Shin, Yeonoh; Hedglin, Mark; Murakami, Katsuhiko S. published the artcile< Structural basis of reiterative transcription from the pyrG and Pyrbi promoters by bacterial RNA polymerase>, HPLC of Formula: 452-06-2, the main research area is gene transcription pyrG Pyrbi bacteria RNA polymerase crystal structure.

Reiterative transcription is a non-canonical form of RNA synthesis by RNA polymerase in which a ribonucleotide specified by a single base in the DNA template is repetitively added to the nascent RNA transcript. We previously determined the X-ray crystal structure of the bacterial RNA polymerase engaged in reiterative transcription from the pyrG promoter, which contains eight poly-G RNA bases synthesized using three C bases in the DNA as a template and extends RNA without displacement of the promoter recognition σ factor from the core enzyme. In this study, we determined a series of transcript initiation complex structures from the pyrG promoter using soak-trigger-freeze X-ray crystallog. We also performed biochem. assays to monitor template DNA translocation during RNA synthesis from the pyrG promoter and in vitro transcription assays to determine the length of poly-G RNA from the pyrG promoter variants. Our study revealed how RNA slips on template DNA and how RNA polymerase and template DNA determine length of reiterative RNA product. Lastly, we determined a structure of a transcript initiation complex at the pyrBI promoter and proposed an alternative mechanism of RNA slippage and extension requiring the σ dissociation from the core enzyme.

Nucleic Acids Research published new progress about Bacillus subtilis. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, HPLC of Formula: 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem