Category: 452-06-2

Prasanthkumar, Kavanal P.; Rayaroth, Manoj P.; Alvarez-Idaboy, Juan R. published the artcile< Insights into the Mechanism of Hydroxyl Radical Mediated Oxidations of 2-Aminopurine: A Computational and Sonochemical Product Analysis Study>, Category: imidazoles-derivatives, the main research area is aminopurine hydroxyl radical mediated oxidation sonochem.

Mechanistic details of hydroxyl radical (•OH) mediated oxidations of 2-aminopurine (2AP) in the aqueous phase have been established in this study via a combination of DFT calculations (at the M05-2X/6-311+G(d,p) level with SMD solvation) and sonochem. end product analyses by the LC-Q-TOF-MS/MS method. Rate constants and branching ratios for single electron transfer (SET), two H-abstractions (HA), and seven radical adduct formation (RAF) reactions of •OH with 2AP were evaluated using transition state theory (TST). The RAF at the C8-position of 2AP is noted as the dominant process, which constitutes almost 46.1% of overall reaction routes. The SET mechanism accounts for the second major pathway (39.6%) followed by RAF at the C6-position (14.3%). Formations of 14 transformation products (TPs, i.e., the nonradical end products) in the sonochem. reactions of •OH with 2AP have been identified by means of the LC-Q-TOF-MS/MS technique. Among the 14 TPs (designated as TP1 to TP14), the lowest and highest mass to charge ratio (m/z) were resp. observed at 129 and 269 in ESI-MS pos. ionization mode. The identities of all TPs have been proposed on the basis of elemental composition of [M + H]+ ions and their resp. MS-MS fragmentation pattern. Four TPs (including guanine) are considered as obtained directly from primary transients by radical elimination, radical-radical combination/disproportionation reactions. The remaining 10 TPs are postulated as a result of successive self- and/or cross-reactions of primary transients/four first generation TPs with reagents such as •OH, O2, and solvent H2O mols.

Journal of Physical Chemistry B published new progress about Collision-induced dissociation. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Category: imidazoles-derivatives.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Zheng, Yangyang; Hong, Kunqiang; Wang, Baowei; Liu, Dingyu; Chen, Tao; Wang, Zhiwen published the artcile< Genetic Diversity for Accelerating Microbial Adaptive Laboratory Evolution>, Application In Synthesis of 452-06-2, the main research area is review accelerating microbial adaptive laboratory genetic diversity; adaptive laboratory evolution; genetic diversity; genome editing; mutant library.

A review. Adaptive laboratory evolution (ALE) is a widely used and highly effective tool for improving microbial phenotypes and investigating the evolutionary roots of biol. phenomena. Serving as the raw materials of evolution, mutations have been extensively utilized to increase the chances of engineering mols. or microbes with tailor-made functions. The generation of genetic diversity is therefore a core technol. for accelerating ALE, and a high-quality mutant library is crucial to its success. Because of its importance, technologies for generating genetic diversity have undergone rapid development in recent years. Here, we review the existing techniques for the construction of mutant libraries, briefly introduce their mechanisms and applications, discuss ongoing and emerging efforts to apply engineering technologies in the construction of mutant libraries, and suggest future perspectives for library construction.

ACS Synthetic Biology published new progress about Alkylating agents. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Application In Synthesis of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Chen, Mingjian; Ma, Changbei; Zhao, Han; Yan, Ying published the artcile< Exonuclease III-assisted fluorometric aptasensor for the carcinoembryonic antigen using graphene oxide and 2-aminopurine>, Recommanded Product: 7H-Purin-2-amine, the main research area is carcinoembryonic antigen exonuclease aptasensor graphene oxide aminopurine; Aptamer; Carcinoembryonic antigen; Enzyme; Fluorescence amplification; Fluorescently labelled probe.

A reliable fluorometric assay is described for the determination carcinoembryonic antigen (CEA) using exonuclease III (Exo III) and a 2-aminopurine binding aptamer. In the absence of CEA, dsDNA is degraded by Exo III, and free 2-AP (which has a blue fluorescence with excitation/emission maxima of 310/365 nm) is released. Strong fluorescence is generated after addition of graphene oxide (GO) to the solution However, the 2-AP modified DNA (T2) cannot be degraded in the presence of CEA by Exo III due to the interaction between CEA and aptamer T1. Hence, only weak fluorescence can be detected after addition of GO. In this system, CEA can be quantified in the 0.05 – 2 ng·mL-1 concentration range with a detection limit of 30 pg·mL-1 (at S/N = 3). The method was successfully applied to analyze serum samples for CEA.

Microchimica Acta published new progress about Aptasensors. 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

Szabla, Rafał; Zdrowowicz, Magdalena; Spisz, Paulina; Green, Nicholas J; Stadlbauer, Petr; Kruse, Holger; Šponer, Jiří; Rak, Janusz published the artcile< 2,6-diaminopurine promotes repair of DNA lesions under prebiotic conditions.>, Electric Literature of 452-06-2, the main research area is .

High-yielding and selective prebiotic syntheses of RNA and DNA nucleotides involve UV irradiation to promote the key reaction steps and eradicate biologically irrelevant isomers. While these syntheses were likely enabled by UV-rich prebiotic environment, UV-induced formation of photodamages in polymeric nucleic acids, such as cyclobutane pyrimidine dimers (CPDs), remains the key unresolved issue for the origins of RNA and DNA on Earth. Here, we demonstrate that substitution of adenine with 2,6-diaminopurine enables repair of CPDs with yields reaching 92%. This substantial self-repairing activity originates from excellent electron donating properties of 2,6-diaminopurine in nucleic acid strands. We also show that the deoxyribonucleosides of 2,6-diaminopurine and adenine can be formed under the same prebiotic conditions. Considering that 2,6-diaminopurine was previously shown to increase the rate of nonenzymatic RNA replication, this nucleobase could have played critical roles in the formation of functional and photostable RNA/DNA oligomers in UV-rich prebiotic environments.

Nature communications published new progress about 452-06-2. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Electric Literature of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Czernecki, Dariusz; Legrand, Pierre; Tekpinar, Mustafa; Rosario, Sandrine; Kaminski, Pierre-Alexandre; Delarue, Marc published the artcile< How cyanophage S-2L rejects adenine and incorporates 2-aminoadenine to saturate hydrogen bonding in its DNA>, Recommanded Product: 7H-Purin-2-amine, the main research area is .

Abstract: Bacteriophages have long been known to use modified bases in their DNA to prevent cleavage by the host′s restriction endonucleases. Among them, cyanophage S-2L is unique because its genome has all its adenines (A) systematically replaced by 2-aminoadenines (Z). Here, we identify a member of the PrimPol family as the sole possible polymerase of S-2L and we find it can incorporate both A and Z in front of a T. Its crystal structure at 1.5 Å resolution confirms that there is no structural element in the active site that could lead to the rejection of A in front of T. To resolve this contradiction, we show that a nearby gene is a triphosphohydolase specific of dATP (DatZ), that leaves intact all other dNTPs, including dZTP. This explains the absence of A in S-2L genome. Crystal structures of DatZ with various ligands, including one at sub-angstrom resolution, allow to describe its mechanism as a typical two-metal-ion mechanism and to set the stage for its engineering.

Nature Communications published new progress about 452-06-2. 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

Nejad, Maryam Imani; Price, Nathan E.; Haldar, Tuhin; Lewis, Calvin; Wang, Yinsheng; Gates, Kent S. published the artcile< Interstrand DNA cross-links derived from reaction of a 2-aminopurine residue with an abasic site>, Electric Literature of 452-06-2, the main research area is interstrand DNA crosslink derived reaction aminopurine abasic.

Efficient methods for the site-specific installation of structurally-defined interstrand crosslinks in duplex DNA may be useful in a wide variety of fields. The work described here developed a high-yield synthesis of chem. stable interstrand crosslinks resulting from a reductive amination reaction between an abasic site and the noncanonical nucleobase 2-aminopurine in duplex DNA. Results from footprinting, LC-MS, and stability studies support the formation of an N2-alkylamine attachment between the 2-aminopurine residue and the Ap site. The reaction performs best when the 2-aminopurine residue on the opposing strand is offset 1 nt to the 5′-side of the abasic site. The crosslink confers substantial resistance to thermal denaturation (melting). The crosslinking reaction is fast (complete in 4 h), employs only com. available reagents, and can be used to generate crosslinked duplexes in sufficient quantities for biophys., structural, and DNA repair studies.

ACS Chemical Biology published new progress about DNA damage. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Electric Literature of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Malina, Jaroslav; Kostrhunova, Hana; Scott, Peter; Brabec, Viktor published the artcile< FeII Metallohelices Stabilize DNA G-Quadruplexes and Downregulate the Expression of G-Quadruplex-Regulated Oncogenes>, Recommanded Product: 7H-Purin-2-amine, the main research area is Fe Metallohelices DNA G quadruplexes oncogenes; DNA; G-quadruplexes; metalo-supramolecular helicates; multitargeted agens; oncogenes.

DNA G-quadruplexes (G4s) have been identified within the promoter regions of many proto-oncogenes. Thus, G4s represent attractive targets for cancer therapy, and the design and development of new drugs as G4 binders is a very active field of medicinal chem. Here, mol. biophysics and biol. methods were employed to investigate the interaction of chiral metallohelices with a series of four DNA G4s (hTelo, c-myc, c-kit1, c-kit2) that are formed by the human telomeric sequence (hTelo) and in the promoter regions of c-MYC and c-KIT proto-oncogenes. We show that the investigated water-compatible, optically pure metallohelices, which are made by self-assembly of simple nonpeptidic organic components around FeII ions and exhibit bioactivity emulating the natural systems, bind with high affinity to G4 DNA and much lower affinity to duplex DNA. Notably, both enantiomers of a metallohelix containing a m-xylenyl bridge (5 b) were found to effectively inhibit primer elongation catalyzed by Taq DNA polymerase by stabilizing G4 structures formed in the template strands containing c-myc and c-kit2 G4-forming sequences. Moreover, both enantiomers of 5 b downregulated the expression of c-MYC and c-KIT oncogenes in human embryonic kidney cells at mRNA and protein levels. As metallohelices also bind alternative nucleic acid structures, they hold promise as potential multitargeted drugs.

Chemistry – A European Journal published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (c-kit1). 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

Yalcin, Abdullah; Sarkici, Gulcin; Kolac, Umut Kerem published the artcile< PKR inhibitors suppress endoplasmic reticulum stress and subdue glucolipotoxicitymediated impairment of insulin secretion in pancreatic beta cells>, Related Products of 452-06-2, the main research area is pancreatic beta cell protein kinase R inhibitor endoplasmic reticulum; ER stress; protein kinase R; β cell degeneration; Type 2 diabetes.

Type 2 diabetes mellitus is characterized by insulin resistance and hypersecretion of insulin from the pancreas to compensate for decreased insulin sensitivity in the peripheral tissues. In later stages of the disease insulin-secreting beta cell degeneration commences and patients require insulin replacement therapy in order to accomplish proper regulation of their blood glucose. Endoplasmic reticulum (ER) stress in the beta cells is one of the factors contributing to this detrimental effect. Protein kinase R (PKR) is a cellular stress kinase activated by ER stress and contributing to degeneration of pancreatic islets. In order to determine whether inhibition of PKR activation by specific small mol. inhibitors of PKR ameliorates pancreatic insulin secretion capacity, we treated beta cells with two imidazole/oxindole-derived inhibitors of PKR kinase, imoxin (C16) and 2-aminopurine (2-AP), in the presence of ER stress. Our results demonstrate that PKR inhibition suppresses tunicamycin-mediated ER stress without altering the insulin production capacity of the cells. Palmitic acid-mediated suppression of insulin secretion, however, was subdued significantly by PKR inhibitor treatment through an ER stress-related mechanism. We suggest that PKR inhibitor treatment may be used to increase the insulin secretion capacity of the pancreas in later stages of diabetes.

Turkish Journal of Biology published new progress about Cell death. 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

Plasser, Felix; Gomez, Sandra; Menger, Maximilian F. S. J.; Mai, Sebastian; Gonzalez, Leticia published the artcile< Highly efficient surface hopping dynamics using a linear vibronic coupling model>, Category: imidazoles-derivatives, the main research area is surface hopping dynamics linear vibronic coupling model.

We report an implementation of the linear vibronic coupling (LVC) model within the surface hopping dynamics approach and present utilities for parameterizing this model in a blackbox fashion. This results in an extremely efficient method to obtain qual. and even semi-quant. information about the photodynamical behavior of a mol., and provides a new route toward benchmarking the results of surface hopping computations. The merits and applicability of the method are demonstrated in a number of applications. First, the method is applied to the SO2 mol. showing that it is possible to compute its absorption spectrum beyond the Condon approximation, and that all the main features and timescales of previous on-the-fly dynamics simulations of intersystem crossing are reproduced while reducing the computational effort by three orders of magnitude. The dynamics results are benchmarked against exact wavepacket propagations on the same LVC potentials and against a variation of the electronic structure level. Four addnl. test cases are presented to exemplify the broader applicability of the model. The photodynamics of the isomeric adenine and 2-aminopurine mols. are studied and it is shown that the LVC model correctly predicts ultrafast decay in the former and an extended excited-state lifetime in the latter. Futhermore, the method correctly predicts ultrafast intersystem crossing in the modified nucleobase 2-thiocytosine and its absence in 5-azacytosine while it fails to describe the ultrafast internal conversion to the ground state in the latter.

Physical Chemistry Chemical Physics published new progress about Absorption spectra. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Category: imidazoles-derivatives.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Mandal, Paulami; De, Debojyoti; Yun, Kyunghee; Kim, Kyeong Kyu published the artcile< Improved differentiation of human adipose stem cells to insulin-producing β-like cells using PDFGR kinase inhibitor Tyrphostin9>, Related Products of 452-06-2, the main research area is human insulin PDFGR kinase inhibitor adipose stem cell; Adipose-derived stem cells; Diabetes mellitus; Differentiation; PDGFR inhibitor; β-cell.

Diabetes mellitus (DM) is a metabolic syndrome where insulin secretion or the response to insulin produced by the body is compromised. The only available long-term treatment is the transplantation of pancreas or islet for procuring β-cells. However, due to the shortage of β-cell sources from the tissues, differentiation of pluripotent stem cells or terminally differentiated cells into β-cell is proposed as an alternative strategy. Previously, human adipose-derived stem cells (ADSCs) were reported to be converted into β-like cells by a stepwise treatment of chems. and growth factors. However, due to the low conversion efficiency, the clin. application was not feasible. In this study, we developed a modified conversion protocol with improved yield and functionality, which is achieved by changing the culture method and addition of Tyrphostin9, a platelet-derived growth factor receptor (PDGFR) kinase inhibitor. Tyrphostin9 was identified from a cell-based chem. screening using the mCherry reporter under the control of the Pdx1 promoter. The β-like cells differentiated under the new protocol showed a 3.6-fold increase in the expression of Pdx1, a marker for pancreatic differentiation, as compared to the previous protocol. We propose that Tyrphostin9 contributes to the β-like cell differentiation by playing a dual role; enhancing the definitive endoderm generation by inhibiting the PI3K signaling and suppressing the taurine-mediated proliferation of definitive endoderm. Importantly, these differentiated cells responded well to low and high glucose stimulations compared to cells differentiated by the previous protocol, as confirmed by the 2.0-fold increase in the C-peptide release. As ADSCs are abundant, easily isolated, and autologous in nature, improved differentiation approaches to generate β-like cells from ADSCs would provide a better opportunity for treating diabetes.

Biochemical and Biophysical Research Communications published new progress about Diabetes mellitus. 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