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Search results for: Adenine

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#33091225   2020/10/22 To Up

Precise Genome Modification in Tomato Using an Improved Prime Editing System.

The CRISPR/Cas-mediated genome editing technology has been widely applied to create knock-out alleles of genes by generating short insertions or deletions (indel) in various plant species. Due to the low efficiency of homology-directed repair (HDR) and difficulties in the delivery of DNA template for HDR, precise genome editing remains challenging in plants (Mao et al., 2019). A tandem repeat-HDR method was developed very recently for sequence replacement in rice, which is most useful for monocots (Lu et al., 2020). Base editors developed from Cas9 nickase fusion with cytosine and adenine deaminases enable targeted C-to-T or A-to-G substitutions, but are restricted to specific types of base replacements and target site selections (Mao et al., 2019).
Yuming Lu, Yifu Tian, Rundong Shen, Qi Yao, Dating Zhong, Xuening Zhang, Jian-Kang Zhu

2006 related Products with: Precise Genome Modification in Tomato Using an Improved Prime Editing System.

1 mg100 μg100 μg100 μg100 μg1 Set1 Set1 Set1 Set100ug

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#33090562   2020/10/22 To Up

The 2-Amino Group of 8-Aza-7-deaza-7-bromopurine-2,6-diamine and Purine-2,6-diamine as Stabilizer for the Adenine-Thymine Base Pair in Heterochiral DNA with Strands in Anomeric Configuration.

Stabilization of DNA is beneficial for many applications in the fields of DNA therapeutics, diagnostics and material science. Now, this phenomenon is studied on heterochiral DNA, an autonomous DNA recognition system with complementary strands in α-D and β-D configuration showing parallel strand orientation. 12-mer heterochiral duplexes were constructed from anomeric (α/β-D) oligonucleotide single-strands. Purine-2,6-diamine and 8-aza-7-deaza-7-bromopurine-2,6-diamine 2'-deoxyribonucleosides having the capability to form tridentate base pairs with dT were used to strengthen the stability of the dA-dT base pair. Tm data and thermodynamic values obtained from UV melting profiles indicated that the 8-aza-7-deaza 2'-deoxyribonucleoside decorated with a bromo substituent is so far the most efficient stabilizer for heterochiral DNA. Compared to that, the stabilizing effect of the purine-2,6-diamine 2'-deoxyribonucleoside is low. Global changes of helix structures were identified by CD-spectra during melting.
Frank Seela, Yingying Chai, Dasharath Kondhare, Aigui Zhang, Peter Leonard

1354 related Products with: The 2-Amino Group of 8-Aza-7-deaza-7-bromopurine-2,6-diamine and Purine-2,6-diamine as Stabilizer for the Adenine-Thymine Base Pair in Heterochiral DNA with Strands in Anomeric Configuration.

11 Set1 Set1 Set

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#33089694   2020/10/22 To Up

Multiscale Conformational Sampling Reveals Excited-State Locality in DNA Self-Repair Mechanism.

Ultraviolet (UV) irradiation is known to be responsible for DNA damage. However, experimental studies in DNA oligonucleotides have shown that UV light can also induce sequence-specific self-repair. Following charge transfer from a guanine adenine sequence adjacent to a cyclobutane pyrimidine dimer (CPD), the covalent bond between the two thymines could be cleaved, recovering the intact base sequence. Mechanistic details promoting the self-repair remained unclear, however. In our theoretical study, we investigated whether optical excitation could directly lead to a charge-transfer state, thereby initiating the repair, or whether the initial excited state remains localized on a single nucleobase. We performed conformational sampling of 200 geometries of the damaged DNA double strand solvated in water and used a hybrid quantum and molecular mechanics approach to compute excited states at the complete active space perturbation level of theory. Analysis of the conformational data set clearly revealed that the excited-state properties are uniformly distributed across the fluctuations of the nucleotide in its natural environment. From the electronic wavefunction, we learned that the electronic transitions remained predominantly local on either adenine or guanine, and no direct charge transfer occurred in the experimentally accessed energy range. The investigated base sequence is not only specific to the CPD repair mechanism but ubiquitously occurs in nucleic acids. Our results therefore give a very general insight into the charge locality of UV-excited DNA, a property that is regarded to have determining relevance in the structural consequences following absorption of UV photons.
Viviana Piccinni, Sebastian Reiter, Daniel Keefer, Regina de Vivie-Riedle

2265 related Products with: Multiscale Conformational Sampling Reveals Excited-State Locality in DNA Self-Repair Mechanism.

100 ug100ug Lyophilized5mg25 inhibitors100 μg500 48 assays100 μg1 ml

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#33089641   2020/10/21 To Up

Nucleoside selectivity of Aspergillus fumigatus nucleoside-diphosphate kinase.

Aspergillus fumigatus infections are rising at a disconcerting rate in tandem with antifungal resistance rates. Efforts to develop novel antifungals has been hindered by the limited knowledge of fundamental biological and structural mechanisms of A. fumigatus propagation. Biosynthesis of NTPs, the building blocks of DNA and RNA, is catalysed by NDK. An essential enzyme in A. fumigatus, NDK poses as an attractive target for novel antifungals. NDK exhibits broad substrate specificity across species, using both purines and pyrimidines, but the selectivity of such nucleosides in A. fumigatus NDK is unknown, impeding structure-guided inhibitor design. Structures of NDK in unbound- and NDP-bound states were solved and NDK activity was assessed in the presence of various NTP substrates. We present the first instance of a unique substrate binding mode adopted by CDP and TDP specific to A. fumigatus NDK that illuminates the structural determinants of selectivity. Analysis of the oligomeric state reveals that A. fumigatus NDK adopts a hexameric assembly in both unbound- and NDP-bound states, contrary to previous reports suggesting it is tetrameric. Kinetic analysis revealed that ATP exhibited the greatest turnover rate (321 ± 33.0 s ), specificity constant (626 ± 110.0 mM s ) and binding free energy change (-37.0 ± 3.5 kcal/mol). Comparatively, cytidine nucleosides displayed the slowest turnover rate (53.1 ± 3.7 s ) and lowest specificity constant (40.2 ± 4.4 mM s ). We conclude that NDK exhibits nucleoside selectivity whereby adenine nucleosides are used preferentially compared to cytidine nucleosides, and these insights can be exploited to guide drug design.
Stephanie Nguyen, Blagojce Jovcevski, Tara L Pukala, John B Bruning

2763 related Products with: Nucleoside selectivity of Aspergillus fumigatus nucleoside-diphosphate kinase.

100ug Lyophilized 0.2 mg 100μl250ul 5 G2 mL250 mg100ul1 mg50 mg100

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#33088686   2020/02/24 To Up

Exploration of 5-cyano-6-phenylpyrimidin derivatives containing an 1,2,3-triazole moiety as potent FAD-based LSD1 inhibitors.

Histone lysine specific demethylase 1 (LSD1) has become a potential therapeutic target for the treatment of cancer. Discovery and develop novel and potent LSD1 inhibitors is a challenge, although several of them have already entered into clinical trials. Herein, for the first time, we reported the discovery of a series of 5-cyano-6-phenylpyrimidine derivatives as LSD1 inhibitors using flavin adenine dinucleotide (FAD) similarity-based designing strategy, of which compound was finally identified to repress LSD1 with IC = 183 nmol/L. Docking analysis suggested that compound fitted well into the FAD-binding pocket. Further mechanism studies showed that compound may inhibit LSD1 activity competitively by occupying the FAD binding sites of LSD1 and inhibit cell migration and invasion by reversing epithelial to mesenchymal transition (EMT). Overall, these findings showed that compound is a suitable candidate for further development of novel FAD similarity-based LSD1 inhibitors.
Liying Ma, Haojie Wang, Yinghua You, Chaoya Ma, Yuejiao Liu, Feifei Yang, Yichao Zheng, Hongmin Liu

2069 related Products with: Exploration of 5-cyano-6-phenylpyrimidin derivatives containing an 1,2,3-triazole moiety as potent FAD-based LSD1 inhibitors.

0.1ml (1mg/ml)200ul50 ug 100ug100ug Lyophilized0.1 mg100ug100ug

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#33087526   2020/10/21 To Up

A Second Riboswitch Class for the Enzyme Cofactor NAD.

A bacterial noncoding RNA motif almost exclusively associated with pnuC genes was uncovered using comparative sequence analysis. Some PnuC proteins are known to transport nicotinamide riboside (NR), which is a component of the ubiquitous and abundant enzyme cofactor nicotinamide adenine dinucleotide (NAD+). Thus, we speculated that the newly found 'pnuC motif' RNAs might function as aptamers for a novel class of NAD+-sensing riboswitches. RNA constructs that encompass the conserved nucleotides and secondary structure features that define the motif indeed selectively bind NAD+, nicotinamide mononucleotide (NMN), and NR. Mutations that disrupt strictly conserved nucleotides of the aptamer also disrupt ligand binding. These bioinformatic and biochemical findings indicate that pnuC motif RNAs are likely members of a second riboswitch class that regulates gene expression in response to NAD+ binding.
Shanker S S Panchapakesan, Lukas Corey, Sarah Malkowski, Gadareth Higgs, Ronald R Breaker

1883 related Products with: A Second Riboswitch Class for the Enzyme Cofactor NAD.

1 mg96T100μg5 ml125 µg100 1,000 tests0.1 mg100ug Lyophilized

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#33087354   2020/10/21 To Up

MCART1/SLC25A51 is required for mitochondrial NAD transport.

The nicotinamide adenine dinucleotide (NAD/NADH) pair is a cofactor in redox reactions and is particularly critical in mitochondria as it connects substrate oxidation by the tricarboxylic acid (TCA) cycle to adenosine triphosphate generation by the electron transport chain (ETC) and oxidative phosphorylation. While a mitochondrial NAD transporter has been identified in yeast, how NAD enters mitochondria in metazoans is unknown. Here, we mine gene essentiality data from human cell lines to identify () as coessential with ETC components. -null cells have large decreases in TCA cycle flux, mitochondrial respiration, ETC complex I activity, and mitochondrial levels of NAD and NADH. Isolated mitochondria from cells lacking or overexpressing have greatly decreased or increased NAD uptake in vitro, respectively. Moreover, and , a yeast mitochondrial NAD transporter, can functionally complement for each other. Thus, we propose that MCART1 is the long sought mitochondrial transporter for NAD in human cells.
Nora Kory, Jelmi Uit de Bos, Sanne van der Rijt, Nevena Jankovic, Miriam Güra, Nicholas Arp, Izabella A Pena, Gyan Prakash, Sze Ham Chan, Tenzin Kunchok, Caroline A Lewis, David M Sabatini

2457 related Products with: MCART1/SLC25A51 is required for mitochondrial NAD transport.

100ug Lyophilized25 μg100ug Lyophilized1 g1 LITRE100ug Lyophilized100ug Lyophilized100ug Lyophilized100 TESTS0.1ml (1mg/ml)25 μg100ug Lyophilized

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#33087267   // To Up

NAD-mediated regulation of mammalian base excision repair.

The enzymes of the base excision repair (BER) pathway form DNA lesion-dependent, transient complexes that vary in composition based on the type of DNA damage. These protein sub-complexes facilitate substrate/product handoff to ensure reaction completion so as to avoid accumulation of potentially toxic DNA repair intermediates. However, in the mammalian cell, additional signaling molecules are required to fine-tune the activity of the BER pathway enzymes and to facilitate chromatin/histone reorganization for access to the DNA lesion for repair. These signaling enzymes include nicotinamide adenine dinucleotide (NAD) dependent poly(ADP-ribose) polymerases (PARP1, PARP2) and class III deacetylases (SIRT1, SIRT6) that comprise a key PARP-NAD-SIRT axis to facilitate the regulation and coordination of BER in the mammalian cell. Here, we briefly describe the key nodes in the BER pathway that are regulated by this axis and highlight the cellular and organismal variation in NAD bioavailability that can impact BER signaling potential. We discuss how cellular NAD is required for BER to maintain genome stability and to mount a robust cellular response to DNA damage. Finally, we consider the dependence of BER on the PARP-NAD-SIRT axis for BER protein complex assembly.
Kate M Saville, Jennifer Clark, Anna Wilk, Gresyn D Rogers, Joel F Andrews, Christopher A Koczor, Robert W Sobol

2828 related Products with: NAD-mediated regulation of mammalian base excision repair.

One 96-Well Microplate Ki 100 gms 25 mg 1 GTwo 96-Well Microplate Ki500 grams100ul500 assays500 MGOne 96-Well Microplate Ki

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#33086058   // To Up

LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1.

Cytosolic proteins are required for regulation of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (Nox) isozymes. Here we show that Src homology 3 (SH3) domain-containing YSC84-like 1 (SH3YL1), as a Nox4 cytosolic regulator, mediates lipopolysaccharide (LPS)-induced HO generation, leading to acute kidney injury. The SH3YL1, Ysc84p/Lsb4p, Lsb3p, and plant FYVE proteins (SYLF) region and SH3 domain of SH3YL1 contribute to formation of a complex with Nox4-p22. Interaction of p22 with SH3YL1 is triggered by LPS, and the complex induces HO generation and pro-inflammatory cytokine expression in mouse tubular epithelial cells. After LPS injection, SH3YL1 knockout mice show lower levels of acute kidney injury biomarkers, decreased secretion of pro-inflammatory cytokines, decreased infiltration of macrophages, and reduced tubular damage compared with wild-type (WT) mice. The results strongly suggest that SH3YL1 is involved in renal failure in LPS-induced acute kidney injury (AKI) mice. We demonstrate that formation of a ternary complex of p22-SH3YL1-Nox4, leading to HO generation, induces severe renal failure in the LPS-induced AKI model.
Jung-Yeon Yoo, Dae Ryong Cha, Borim Kim, Eun Jung An, Sae Rom Lee, Jin Joo Cha, Young Sun Kang, Jung Yeon Ghee, Jee Young Han, Yun Soo Bae

2129 related Products with: LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1.

96T50 ul100ug Lyophilized100ug Lyophilized100ug Lyophilized100 ul100ug Lyophilized100 ul100ug Lyophilized100ug Lyophilized50 ul100ug Lyophilized

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#33084596   // To Up

Tumour initiation, store-operated calcium entry (SOCE) and apoptosis: cyclic nucleotide dependence.

Chemical instigators and modulators of tumourigenesis influence cell signal transduction pathways. Cyclic nucleotides and steroid hormones may contribute to the process of carcinogenesis or provide protection via apoptotic mechanisms. Although several pharmacologic classes of compounds influence cyclic nucleotide levels markedly, less is known about the class effects of promoters and blockers of tumourigenesis and apoptosis. This molecular modeling study uses cyclic nucleotide templates to investigate relative molecular similarity within compounds modulating tumourigenesis and apoptosis. Findings, in respect of superimposition and molecular fit of the investigated compounds, are related to their individual effects on cyclic nucleotide pharmacology. Modulators of tumourigenesis and estrogen receptor sub-type ligands relate to cyclic nucleotide structure. Estradiol and GPER ligands provide a similar pattern of fit to adenine nucleotide. Chemically diverse modulators of apoptosis, including K+ channel ligands, fit to different components of cyclic nucleotide structure. Compounds modulating Ca2+ entry and IP3 receptors relate structurally to the nucleotide dioxaphosphinin moiety. Relative molecular similarity within the structures of apoptosis and tumourigenesis modulators identifies a unifying property within chemically disparate compounds. The ubiquitous generation of oxidative stress and ROS in cells by apoptosis modulating compounds may relate to the disruption of cyclic nucleotide regulated homeostasis mechanisms.
Wynford R Williams

2154 related Products with: Tumour initiation, store-operated calcium entry (SOCE) and apoptosis: cyclic nucleotide dependence.

100ug Lyophilized10 mg100 plates 5 G 1 kit(s) 400 assays100ug Lyophilized 5 G0.5 mg100ug1 kit96 rxns

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