- Live-Cell Protein Modification by Boronate-Assisted Hydroxamic Acid Catalysis
-
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
-
supporting information
p. 14976 - 14980
(2021/09/29)
-
- ANILINE DERIVATIVES,THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
-
The present invention relates to aniline derivatives, to their preparation and to their therapeutic application.
- -
-
Page/Page column 124
(2013/03/28)
-
- NK-1 AND SEROTONIN TRANSPORTER INHIBITORS
-
The invention encompasses compounds of Formula I, including pharmaceutically acceptable salts, their pharmaceutical compositions, and their use in treating disorders associated with an excess or imbalance of tachykinins or serotonin or both.
- -
-
Page/Page column 88
(2010/11/28)
-
- Design, synthesis, anti-HIV activities, and metabolic stabilities of alkenyldiarylmethane (ADAM) non-nucleoside reverse transcriptase inhibitors
-
The alkenyldiarylmethane (ADAM) HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) are effective anti-HIV agents in cell culture. However, the potential clinical utility of the ADAMs is expected to be limited by the presence of methyl ester mo
- Silvestri, Maximilian A.,Nagarajan, Muthukaman,De Clercq, Erik,Pannecouque, Christophe,Cushman, Mark
-
p. 3149 - 3162
(2007/10/03)
-