An Electrochemical Approach for the Synthesis of Perfluoroalkylated Purine and Indole Analogues of Plant Growth Regulators

Médebielle, Maurice; Fujii, Shozo; Kato, Katsuya

doi:10.1016/s0040-4020(00)00154-x

Cited by 38 publications

(13 citation statements)

References 45 publications

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“…This purine analogue was first synthesized in 1958 as a potential anticancer agent, and in the late 1980s and early 1990s, the compound was used as a reactant for designing arrhythmia and antiviral drugs as well as compounds set to regulate plant growth2627. For over 20 years, F2124–0890 was seldom reported in the literature until in 2014 when it was identified as an inhibitor of SARS-CoV 3CLpro by Lee et al 28…”

Section: Discussionmentioning

confidence: 99%

X-ray Structure and Enzymatic Activity Profile of a Core Papain-like Protease of MERS Coronavirus with utility for structure-based drug design

Clasman

Báez-Santos

Mettelman

et al. 2017

Sci Rep

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Ubiquitin-like domain 2 (Ubl2) is immediately adjacent to the N-terminus of the papain-like protease (PLpro) domain in coronavirus polyproteins, and it may play a critical role in protease regulation and stability as well as in viral infection. However, our recent cellular studies reveal that removing the Ubl2 domain from MERS PLpro has no effect on its ability to process the viral polyprotein or act as an interferon antagonist, which involves deubiquitinating and deISGylating cellular proteins. Here, we test the hypothesis that the Ubl2 domain is not required for the catalytic function of MERS PLpro in vitro. The X-ray structure of MERS PLpro-∆Ubl2 was determined to 1.9 Å and compared to PLpro containing the N-terminal Ubl2 domain. While the structures were nearly identical, the PLpro-∆Ubl2 enzyme revealed the intact structure of the substrate-binding loop. Moreover, PLpro-∆Ubl2 catalysis against different substrates and a purported inhibitor revealed no differences in catalytic efficiency, substrate specificity, and inhibition. Further, no changes in thermal stability were observed between enzymes. We conclude that the catalytic core of MERS PLpro, i.e. without the Ubl2 domain, is sufficient for catalysis and stability in vitro with utility to evaluate potential inhibitors as a platform for structure-based drug design.

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Section: Discussionmentioning

confidence: 99%

X-ray Structure and Enzymatic Activity Profile of a Core Papain-like Protease of MERS Coronavirus with utility for structure-based drug design

Clasman

Báez-Santos

Mettelman

et al. 2017

Sci Rep

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show abstract

“…As a mode of action, this compound acts as a competitive inhibitor against MERS-CoV with an IC 50 value of 6.0 mM, while acts as an allosteric inhibitor against SARS-CoV (IC 50 11 mM). Compound 48 was first synthesized in 1958 as a potential anticancer agent, and in the late 1980s and early 1990s, the compound was used as a reactant for designing arrhythmia and antiviral drugs as well as compounds set to regulate plant growth [97,98].…”

Section: Mers-cov and Sars-cov Pl Proteases Inhibitorsmentioning

confidence: 99%

Recent discovery and development of inhibitors targeting coronaviruses

Pillaiyar

Meenakshisundaram²,

Manickam

2020

Drug Discovery Today

329

323

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“…These substitution products were shown to act as analogues of plant growth regulators (eq. 79) [167].…”

Section: Perfluoroalkyl Halides and Related Compoundsmentioning

confidence: 99%

Strategies in Synthetic Radical Organic Chemistry. Recent Advances on Cyclization and SRN1 Reactions

Rossi¹,

Peñéñory

2006

COS

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An Electrochemical Approach for the Synthesis of Perfluoroalkylated Purine and Indole Analogues of Plant Growth Regulators

Cited by 38 publications

References 45 publications

X-ray Structure and Enzymatic Activity Profile of a Core Papain-like Protease of MERS Coronavirus with utility for structure-based drug design

X-ray Structure and Enzymatic Activity Profile of a Core Papain-like Protease of MERS Coronavirus with utility for structure-based drug design

Recent discovery and development of inhibitors targeting coronaviruses

Strategies in Synthetic Radical Organic Chemistry. Recent Advances on Cyclization and SRN1 Reactions

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