- Tag-Free Internal RNA Labeling and Photocaging Based on mRNA Methyltransferases
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The mRNA modification N6-methyladenosine (m6A) is associated with multiple roles in cell function and disease. The methyltransferases METTL3-METTL14 and METTL16 act as “writers” for different target transcripts and sequence motifs. The modification is perceived by dedicated “reader” and “eraser” proteins, but not by polymerases. We report that METTL3-14 shows remarkable cosubstrate promiscuity, enabling sequence-specific internal labeling of RNA without additional guide RNAs. The transfer of ortho-nitrobenzyl and 6-nitropiperonyl groups allowed enzymatic photocaging of RNA in the consensus motif, which impaired polymerase-catalyzed primer extension in a reversible manner. METTL16 was less promiscuous but suitable for chemo-enzymatic labeling using different types of click chemistry. Since both enzymes act on distinct sequence motifs, their combination allowed orthogonal chemo-enzymatic modification of different sites in a single RNA.
- Ovcharenko, Anna,Weissenboeck, Florian P.,Rentmeister, Andrea
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Read Online
- Photoactivatable prodrugs of highly potent duocarmycin analogues for a selective cancer therapy
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A main problem of common cancer chemotherapy is the occurrence of severe side effects caused by insufficient selectivity of the applied drugs. A possible concept to overcome this limitation is light-driven prodrug monotherapy. The synthesis as well as photochemical and biological evaluation of new photoactivatable prodrugs is described. Best results were obtained with prodrug (S,S)-7 a. The photochemical labile protecting groups in (S,S)-7 a can easily be removed by irradiation with UV-A light in 30 min with a power of only 2 J cm-2. The determination of the in vitro cytotoxicity by using an HTCFA-test reveals a QIC50 value of 8200 and the prodrug is more than two million times less cytotoxic than the corresponding seco-drug (-)-(S,S)-5 with an IC50 value of about 110 fM. The big therapeutic window makes (S,S)-7 a very suitable for its use in selective cancer therapy. Copyright
- Tietze, Lutz F.,Müller, Michael,Duefert, Svenia-C.,Schmuck, Kianga,Schuberth, Ingrid
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Read Online
- Metal–Organic Framework-Encapsulated CoCu Nanoparticles for the Selective Transfer Hydrogenation of Nitrobenzaldehydes: Engineering Active Armor by the Half-Way Injection Method
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A novel armor-type composite of metal–organic framework (MOF)-encapsulated CoCu nanoparticles with a Fe3O4 core (Fe3O4@SiO2-NH2-CoCu@UiO-66) has been designed and synthesized by the half-way injection method, which successfully serves as an efficient and recyclable catalyst for the selective transfer hydrogenation. In this half-way injection approach, the pre-synthetic Fe3O4@SiO2-NH2-CoCu was injected into the UiO-66 precursor solution halfway through the MOF budding period. The formed MOF armor could play a role of providing significant additional catalytic sites besides CoCu nanoparticles, protecting CoCu nanoparticles, and improving the catalyst stability, thus facilitating the selective transfer hydrogenation of nitrobenzaldehydes into corresponding nitrobenzyl alcohols in high selectivity (99 %) and conversion (99 %) rather than nitro group reduction products. Notably, this method achieves the precise assembly of a MOF-encapsulated composite, and the ingenious combination of MOF and nanoparticles exhibits excellent catalytic performance in the selective hydrogen transfer reaction, implementing a “1+1>2” strategy in catalysis.
- Li, Yang,Li, Yu-Nong,Zheng, Jian-wei,Dong, Xiao-yun,Guo, Rong-xiu,Wang, Yi-ming,Hu, Ze-nan,Ai, Yongjian,Liang, Qionglin,Sun, Hong-bin
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supporting information
p. 1080 - 1087
(2020/12/18)
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- Utilization of a Hydrogen Source from Renewable Lignocellulosic Biomass for Hydrogenation of Nitroarenes
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Exploring of hydrogen source from renewable biomass, such as glucose in alkaline solution, for hydrogenation reactions had been studied since 1860s. According to proposed pathway, only small part of hydrogen source in glucose was utilized. Herein, the utilization of a hydrogen source from renewable lignocellulosic biomass, one of the most abundant renewable sources in nature, for a hydrogenation reaction is described. The hydrogenation is demonstrated by reduction of nitroarenes to arylamines in up to 95 % yields. Mechanism studies suggest that the hydrogenation occurs via a hydrogen transformation pathway.
- Tan, Fang-Fang,Tang, Kai-Li,Zhang, Ping,Guo, Yan-Jun,Qu, Mengnan,Li, Yang
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p. 4189 - 4195
(2019/03/07)
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- Photocaged Carbohydrates: Versatile Tools for Controlling Gene Expression by Light
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The control of biological processes plays a central role in life science, especially the tight regulation of gene expression for biotechnological systems. In this context, optogenetic tools have emerged as an important instrument for controlling gene expression by light with high spatiotemporal resolution in a non-invasive way. Here, we present the syntheses and characterization of biofunctional photocaged carbohydrates, on the basis of the biologically most relevant carbohydrates glucose, galactose, rhamnose, and lactose. The single-step cleavage of these compounds allows both, to rapidly activate and temporary or permanently repress the transcription in E. coli after short UV-A light exposure. This study thus presents a versatile toolbox of photocaged carbohydrates for the light-triggered regulation and control of cellular processes useful for synthetic bio(techno)logy applications.
- Bier, Claus,Binder, Dennis,Drobietz, Dagmar,Loeschcke, Anita,Drepper, Thomas,Jaeger, Karl-Erich,Pietruszka, J?rg
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- Metal- and Protection-Free [4 + 2] Cycloadditions of Alkynes with Azadienes: Assembly of Functionalized Quinolines
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A base promoted, protection-free, and regioselective synthesis of highly functionalized quinolines via [4 + 2] cycloaddition of azadienes (generated in situ from o-aminobenzyl alcohol) with internal alkynes has been discovered. The reaction tolerates a wide variety of functional groups which has been successfully extended with diynes, (2-aminopyridin-3-yl)methanol, and 1,4-bis(phenylethynyl)benzene to afford (Z)-phenyl-2-styrylquinolines, phenylnaphthyridine, and alkyne-substituted quinolines, respectively. The proposed mechanism and significant role of the solvent were well supported by isolating the azadiene intermediate and deuterium-labeling studies.
- Saunthwal, Rakesh K.,Patel, Monika,Verma, Akhilesh K.
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supporting information
p. 2200 - 2203
(2016/06/01)
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- Regioselective Synthesis of C-3-Functionalized Quinolines via Hetero-Diels-Alder Cycloaddition of Azadienes with Terminal Alkynes
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A highly efficient metal and protection-free approach for the regioselective synthesis of C-3-functionalized quinolines from azadienes (in situ generated from 2-aminobenzyl alcohol) and terminal alkynes through [4 + 2] cycloaddition has been developed. An unprecedented reaction of 2-aminobenzyl alcohol with 1,3- and 1,4-diethynylbenzene provided the C-3 tolylquinolines via [4 + 2] HDA and oxidative decarboxylation. The -NH2 group directed mechanistic approach was well supported by the control experiments and deuterium-labeling studies and by isolating the azadiene intermediate. The reactivity and selectivity of unprotected azadiene in metal-free base-assisted hetero-Diels-Alder reaction is exploited to quickly assemble an important class of C-3-functionalized quinolines, which are difficult to access.
- Saunthwal, Rakesh K.,Patel, Monika,Verma, Akhilesh K.
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p. 6563 - 6572
(2016/08/16)
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- Zinc phthalocyanine with PEG-400 as a recyclable catalytic system for selective reduction of aromatic nitro compounds
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Zinc phthalocyanine with PEG-400 was established as a catalytic system for chemo and regioselective reduction of aromatic nitro compounds to corresponding amines. A large range of reducible functional groups such as acid, amide, ester, halogen, lactone, nitrile, N-benzyl, O-benzyl, hydroxy and heterocycles were well tolerated. Direct synthesis of benzotriazole from O-dinitrobenzene was achieved for the first time. The present catalytic system was successfully employed for the reduction of carbonyl and ester compounds to corresponding alcohols and reductive amination of benzaldehydes with primary amines to form corresponding secondary amines. Remarkable advantages of the present catalytic method include low loading of metal, avoidance of toxic ligands and high isolated yields. The catalyst was recyclable up to four times without any loss of selectivity and activity.
- Sharma, Upendra,Kumar, Neeraj,Verma, Praveen Kumar,Kumar, Vishal,Singh, Bikram
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supporting information; experimental part
p. 2289 - 2293
(2012/09/10)
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- Nickel phthalocyanine assisted highly efficient and selective carbonyl reduction in polyethylene glycol-400
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Nickel phthalocyanine with polyethylene glycol- 400 is described as a reusable green catalytic system for highly chemo- and regioselective reduction of carbonyl compounds to corresponding alcohols at room temperature. The catalytic system showed wide substrate scope covering aromatic, hetero aromatic and aliphatic carbonyl compounds with high turnover number and frequency. In the present study, 1,3- and 1,4-benzenedicarbaldehydes have been regioselectively reduced to corresponding alcohols for the first time. The catalyst was reused up to seven times without any significance loss in activity. Springer Science+Business Media, LLC 2012.
- Verma, Praveen Kumar,Sharma, Upendra,Kumar, Neeraj,Bala, Manju,Kumar, Vishal,Singh, Bikram
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experimental part
p. 907 - 913
(2012/10/07)
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- Synthesis and in vitro antibacterial activity of gemifloxacin derivatives containing a substituted benzyloxime moiety
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A series of novel gemifloxacin (GMFX) derivatives containing a substituted benzyloxime moiety with remarkable improvement in lipophilicity were synthesized. The target compounds evaluated for their in vitro antibacterial activity against representative strains. Our results reveal that most of the target compounds have considerable potency against all of the tested Gram-positive strains including MRSA and MRSE (MIC: 90: 1 μg/mL) is 8-fold more active than GMFX, and 2-fold more active than GMFX and moxifloxacin against MRSE clinical isolates (MIC90: 4 μg/mL). Crown Copyright
- Feng, Lianshun,Lv, Kai,Liu, Mingliang,Wang, Shuo,Zhao, Jing,You, Xuefu,Li, Sujie,Cao, Jue,Guo, Huiyuan
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p. 125 - 136
(2012/11/07)
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- Synthesis and biological activity of pyridopyridazin-6-one p38α MAP kinase inhibitors. Part 2
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This manuscript concludes the Structure Activity Relationship (SAR) on the pyridazinone scaffold and identifies a compound with subnanomolar p38α activity and 24 h coverage in the rat arthritis efficacy model.
- Tynebor, Robert M.,Chen, Meng-Hsin,Natarajan, Swaminathan R.,O'Neill, Edward A.,Thompson, James E.,Fitzgerald, Catherine E.,O'Keefe, Stephen J.,Doherty, James B.
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p. 5971 - 5975
(2012/11/07)
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