- Live-Cell Protein Modification by Boronate-Assisted Hydroxamic Acid Catalysis
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Selective methods for introducing protein post-translational modifications (PTMs) within living cells have proven valuable for interrogating their biological function. In contrast to enzymatic methods, abiotic catalysis should offer access to diverse and new-to-nature PTMs. Herein, we report the boronate-assisted hydroxamic acid (BAHA) catalyst system, which comprises a protein ligand, a hydroxamic acid Lewis base, and a diol moiety. In concert with a boronic acid-bearing acyl donor, our catalyst leverages a local molarity effect to promote acyl transfer to a target lysine residue. Our catalyst system employs micromolar reagent concentrations and affords minimal off-target protein reactivity. Critically, BAHA is resistant to glutathione, a metabolite which has hampered many efforts toward abiotic chemistry within living cells. To showcase this methodology, we installed a variety of acyl groups inE. colidihydrofolate reductase expressed within human cells. Our results further establish the well-known boronic acid-diol complexation as abona fidebio-orthogonal reaction with applications in chemical biology and in-cell catalysis.
- Adamson, Christopher,Kajino, Hidetoshi,Kanai, Motomu,Kawashima, Shigehiro A.,Yamatsugu, Kenzo
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p. 14976 - 14980
(2021/09/29)
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- Precious metal complexes of bis(pyridyl)allenes: Synthesis and catalytic and medicinal applications
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The incorporation of donor-type substituents on the allene core opens up the possibility of coordination complexes in which the metal is bonded to the donor groups, with or without interaction with the double bond system. Despite the challenges in the syn
- Arnau Del Valle, Carla,Maliszewska, Hanna K.,Marín, María J.,Mu?oz, María Paz,Waller, Zo? A. E.,Xia, Ying
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supporting information
p. 16739 - 16750
(2021/12/08)
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- A THERANOSTIC PROBE AND ITS USE FOR TARGETING AND/OR LABELING THE EGFR KINASE AND/OR THE CELLS EXPRESSING EGFR OR ITS FAMILY MEMBERS
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The present application is directed to a theranostic probe and its use for targeting and/or labeling the EGFR kinase and/or the cells expressing EGFR or its family members.
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- Exploring endoperoxides as a new entry for the synthesis of branched azasugars
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A new class of nitrogen-containing endoperoxides were synthesised by a photochemical [4 + 2]-cycloaddition between a diene and singlet oxygen. The endoperoxides were dihydroxylated and protected to provide a series of endoperoxide building blocks for organic synthesis, with potential use as precursors for the synthesis of branched azasugars. Preliminary exploration of the chemistry of these building blocks provided access to a variety of derivatives including tetrahydrofurans, epoxides and protected amino-tetraols.
- Domeyer, Svenja,Bjerregaard, Mark,Johansson, Henrik,Pedersen, Daniel Sejer
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p. 644 - 647
(2017/06/20)
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- Synthesis of Vinyl Isocyanides and Development of a Convertible Isonitrile
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The reaction of isocyanomethylenetriphenylphosphorane, generated in situ from the corresponding phosphonium salt, with a diverse set of aldehydes afforded vinyl isocyanides in good to high yields. Excellent E-selectivity was observed for aliphatic aldehydes and 2,6-disubstituted aromatic aldehydes, whereas Z-olefins were formed predominantly with ortho-substituted aryl aldehydes. (Z)-1-Bromo-2-(2-isocyanovinyl)benzene (5l) was found to be a truly universal isonitrile since, after Ugi reaction, the resulting secondary amide unit (RNHCO-) is convertible under both acidic and basic conditions. The application of 5l in the synthesis of polyheterocycles is also illustrated.
- Spallarossa, Martina,Wang, Qian,Riva, Renata,Zhu, Jieping
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p. 1622 - 1625
(2016/05/02)
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- Compounds and methods for protease detection
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Alternative methods for the detection and measurement of proteases in biological samples and compounds which allow for such detection are required to allow for rapid and selective identification of these enzymes. Compounds which allow for selective identification of these enzymes are provided with assays and kits for their use.
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- Enantioselective NHC-Catalyzed Redox [4 + 2]-Hetero-Diels-Alder Reactions Using α,β-Unsaturated Trichloromethyl Ketones as Amide Equivalents
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α,β-Unsaturated trichloromethyl ketones are suitable α,β-unsaturated amide and ester equivalents in N-heterocyclic carbene (NHC)-catalyzed redox hetero-Diels-Alder reactions with azolium enolates generated from α-aroyloxyaldehydes. The initially formed syn-dihydropyranone products can be isolated or can undergo ring-opening with benzylamine followed by aminolysis of the resulting CCl3 ketone to form a range of diamides with high diastereo- and enantioselectivity (up to >95:5 dr and >99% ee).
- Attaba, Nassilia,Taylor, James E.,Slawin, Alexandra M. Z.,Smith, Andrew D.
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p. 9728 - 9739
(2015/10/12)
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- Synthesis of phosphorus isosters of β-amyloid peptides fragments
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We have developed a synthetic route to pseudo dipeptides, analogs of certain fragments of β-amyloid peptides (products of the APP protein hydrolysis). These compounds can be used for preparation of phosphinic acidic oligopeptides representing the peptide sequence of the β-amyloid but containing the phosphorus isoster peptide fragment. Synthesis of pseudo ornityl-glutamate, pseudo arginyl-glutamate, pseudo glycyl-leucine, and pseudo isoleucyl-glycine via amino- and amidoalkylation of phosphonic acids containing the structural isoster of the corresponding amino acid is described.
- Dmitriev,Ragulin
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p. 2091 - 2098
(2015/11/02)
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- AZABENZIMIDAZOLES AS RESPIRATORY SYNCYTIAL VIRUS ANTIVIRAL AGENTS
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A compound satisfying formula I, a prodrug, N-oxide, addition salt, quaternary metal complex, or a stereochemically isomeric form thereof; (formula I) compositions contain these compounds as active ingredient and processes for preparing these compounds and compositions.
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- MODULATORS OF HISTONE METHYLTRANSFERASE, AND METHODS OF USE THEREOF
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Disclosed are compounds, pharmaceutical compositions containing the compounds, and the uses of the compounds and compositions as modulators of histone methyltransferases, and for treating diseases influenced by modulation of histone methyltransferase activity.
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- AMD070, a CXCR4 chemokine receptor antagonist: Practical large-scale laboratory synthesis
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An efficient and convergent four-step synthetic route to the CXCR4 chemokine receptor antagonist AMD070 (1) has been developed which employs only a single chromatographic step in the entire sequence. Novel reductive amination methods have been developed for the coupling of 2 and 3 in which a dehydrative imine formation is followed by reduction with an attenuated borohydride reagent (zinc chloride and sodium borohydride). Selective extraction methods were employed to purify synthetic intermediates and remove reagents and impurities. A procedure has also been developed to isolate 1 in a pure crystalline form.
- Crawford, Jason B.,Chen, Gang,Gauthier, David,Wilson, Trevor,Carpenter, Bryon,Baird, Ian R.,McEachern, Ernie,Kaller, Alan,Harwig, Curtis,Atsma, Bem,Skerlj, Renato T.,Bridger, Gary J.
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p. 823 - 830
(2013/01/03)
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- Histamine H2-receptor agonists. Synthesis, in vitro pharmacology, and qualitative structure-activity relationships of substituted 4- and 5-(2- aminoethyl)thiazoles
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It is well known that both histamine and dimaprit show moderate histamine H2-receptor agonistic activities on the guinea pig right atrium. Quantum chemical calculations on these two compounds showed similarities in electron distributions and molecular electrostatic potentials (MEP's), which could be extended to rigid analogues [2-amino-5-(2-aminoethyl)thiazoles] of the latter structure. On the base of these results a series of substituted 4- and 5-(2- aminoethyl)thiazoles was synthesized applying small alkyl substitution variations as reported for histamine. 2-Amino-5-(2-aminoethyl)-4- methylthiazole (Amthamine) proved to be the most potent full histamine H2- receptor agonist on the guinea pig right atrium, being with a pD2 value of 6.21 slightly more potent than histamine. This compound shows no affinity for H1-receptors and is a full but weak agonist on the histamine H3-receptor with a pD2 value of 4.70, thus showing a marked specificity for histamine H2-receptors. In the 5-(2-aminoethyl)thiazole series the presence of a 2- amino substituent proved to be not essential for stimulation of the histamine H2-receptor, leading to the important conclusion that in contrast to histamine, for this series, acceptance of a proton by the thiazole nucleus of the agonist from the active site of the receptor is sufficient for the stimulation of the histamine H2-receptor.
- Eriks,Van der Goot,Sterk,Timmerman
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p. 3239 - 3246
(2007/10/02)
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- Synthesis of Phosphonopeptides as Thrombin Inhibitors
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Synthesis of phosphonopeptides 1 and their inhibitory activity of thrombin are described.
- Wang, Chia-Lin J.,Taylor, Thelma L.,Mical, Alfred J.,Spitz, Susan,Reilly, Thomas M.
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p. 7667 - 7670
(2007/10/02)
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- INDOLE DERIVATIVES. 126. SUBSTITUTED NITROTRIPTAMINES
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A preparative method has been developed for obtaining substituted nitrotryptamines from the corresponding nitrophenylhydrazones of γ-phtalimidobutyraldehyde.
- Vinograd, L. Kh.,Suvorov, N. N.
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p. 984 - 988
(2007/10/02)
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