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November 24, 2016
Very Important Paper: Exploring the Potent Inhibition of CTP Synthase by Gemcitabine-5'-Triphosphate
Gregory D. McCluskey, Samy Mohamady, Scott D. Taylor, Stephen L. Bearne*
The nucleoside analogue gemcitabine is used as a chemotherapy drug to treat lung, pancreatic, bladder, and breast cancers. One metabolite of this drug, gemcitabine-5'-triphosphate, is believed to deplete intracellular CTP levels by inhibiting CTP synthase, but the direct inhibition of this enzyme had not been demonstrated. Now, S.L. Bearne (Dalhousie University, Canada) and co-workers show that gemcitabine-5'-triphosphate is indeed a potent competitive inhibitor of Escherichia coli CTP synthase. Remarkably, the enzyme also acts on an abundant catabolite of the drug, 2',2'-difluoro-2'-deoxyuridine-5'-triphosphate, to convert it back to gemcitabine-5'-triphosphate, suggesting that CTP synthase may play a role in replenishing the active drug in vivo.
Recently Published Articles
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Version of Record online: 5 DEC 2016 | DOI: 10.1002/cbic.201600524
I spy: Monitoring cysteine reactivity directly in living cells allows the elucidation of the sites of cysteine modification by oxidants as well as endogenous and exogenous thiol-reactive agents. We evaluated a panel of caged electrophiles as live-cell compatible cysteine-reactive probes and report an optimized probe for enhanced labeling of cellular cysteines.
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Aem Nuylert, Yuko Ishida and Yasuhisa Asano
Accepted manuscript online: 3 DEC 2016 03:50AM EST | DOI: 10.1002/cbic.201600447
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Version of Record online: 2 DEC 2016 | DOI: 10.1002/cbic.201600422
Polymeric guanidinoglycoside vehicles: Comparing the cellular uptake of undecorated PAMAM dendrimers with that of PAMAM-neomycin and -guanidinoneomycin conjugates shows that the presence of guanidinoneomycins, to a greater extent than that of neomycins, plays an important role in promoting cellular uptake of high-molecular-weight cargos.
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Leon Fürtges, David Conradt, Dr. Michael A. Schätzle, Shailesh Kumar Singh, Dr. Nada Kraševec, Prof. Dr. Tea Lanišnik Rižner, Prof. Dr. Michael Müller and Dr. Syed Masood Husain
Version of Record online: 1 DEC 2016 | DOI: 10.1002/cbic.201600489
Not a common transformation: The physiological function of 17β-hydroxysteroid dehydrogenase from the filamentous fungus Curvularia lunata (teleomorph Cochliobolus lunatus) is proposed as being an NADPH-dependent reduction of a polyhydroxyanthracene. With a substrate range from steroids to polyhydroxynaphthalenes, it might be seen as part of a diverse biosynthetic matrix.