Crystal-structure-based design and synthesis of benz[cd]indole-containing inhibitors of thymidylate synthase

1992 ◽  
Vol 35 (4) ◽  
pp. 663-676 ◽  
Author(s):  
Michael D. Varney ◽  
Gifford P. Marzoni ◽  
Cindy L. Palmer ◽  
Judith G. Deal ◽  
Stephanie Webber ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Thymidylate Synthase ◽  
Design And Synthesis

Design, Synthesis, and X-ray Crystal Structure of a Potent Dual Inhibitor of Thymidylate Synthase and Dihydrofolate Reductase as an Antitumor Agent1

2000 ◽  
Vol 43 (21) ◽  
pp. 3837-3851 ◽  
Author(s):  
Aleem Gangjee ◽  
Jianming Yu ◽  
John J. McGuire ◽  
Vivian Cody ◽  
Nikolai Galitsky ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Dihydrofolate Reductase ◽  
Thymidylate Synthase ◽  
Dual Inhibitor ◽  
Design Synthesis ◽  
X Ray

scholarly journals A Dendralenic C–H Acid

Synlett ◽  
2019 ◽  
Vol 30 (04) ◽  
pp. 433-436 ◽  
Author(s):  
Denis Höfler ◽  
Richard Goddard ◽  
Nils Nöthling ◽  
Benjamin List
Keyword(s):  
Crystal Structure ◽  
Acid Catalysis ◽  
Bronsted Acid ◽  
Brønsted Acid ◽  
Design And Synthesis ◽  
Brönsted Acid ◽  
Bronsted Acid Catalysis

The design and synthesis of a strong, dendralenic C–H acid is described. Crystal structure analyses confirm the proposed structure. Despite the moderate stability of our motif, an application to Brønsted acid catalysis has been explored.

The crystal structure of thymidylate synthase from Pneumocystis carinii reveals a fungal insert important for drug design

2000 ◽  
Vol 297 (3) ◽  
pp. 645-657 ◽  
Author(s):  
Amy C Anderson ◽  
Kathy M Perry ◽  
Douglas M Freymann ◽  
Robert M Stroud
Keyword(s):  
Crystal Structure ◽  
Drug Design ◽  
Thymidylate Synthase ◽  
Pneumocystis Carinii

scholarly journals Design and Synthesis of N-phenyl Phthalimides as Potent Protoporphyrinogen Oxidase Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4363
Author(s):  
Wei Gao ◽  
Xiaotian Li ◽  
Da Ren ◽  
Susu Sun ◽  
Jingqian Huo ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Enzyme Activity ◽  
Molecular Docking ◽  
Molecular Design ◽  
Design Strategy ◽  
Docking Studies ◽  
Activity Assay ◽  
Enzyme Activity Assay ◽  
Protoporphyrinogen Oxidase ◽  
Design And Synthesis

Protoporphyrinogen oxidase (PPO) has been identified as one of the most promising targets for herbicide discovery. A series of novel phthalimide derivatives were designed by molecular docking studies targeting the crystal structure of mitochondrial PPO from tobacco (mtPPO, PDB: 1SEZ) by using Flumioxazin as a lead, after which the derivatives were synthesized and characterized, and their herbicidal activities were subsequently evaluated. The herbicidal bioassay results showed that compounds such as 3a (2-(4-bromo-2,6-difluorophenyl) isoindoline-1,3-dione), 3d (methyl 2-(4-chloro-1,3-dioxoisoindolin-2-yl)-5-fluorobenzoate), 3g (4-chloro-2-(5-methylisoxazol-3-yl) isoindoline-1,3-dione), 3j (4-chloro-2-(thiophen-2-ylmethyl) isoindoline-1,3-dione) and 3r (2-(4-bromo-2,6-difluorophenyl)-4-fluoroisoindoline-1,3-dione) had good herbicidal activities; among them, 3a showed excellent herbicidal efficacy against A. retroflexus and B. campestris via the small cup method and via pre-emergence and post-emergence spray treatments. The efficacy was comparable to that of the commercial herbicides Flumioxazin, Atrazine, and Chlortoluron. Further, the enzyme activity assay results suggest that the mode of action of compound 3a involves the inhibition of the PPO enzyme, and 3a showed better inhibitory activity against PPO than did Flumioxazin. These results indicate that our molecular design strategy contributes to the development of novel promising PPO inhibitors.

Crystal-Structure-Based Design and Synthesis of Novel C-Terminal Inhibitors of HIV Protease

1994 ◽  
Vol 37 (15) ◽  
pp. 2274-2284 ◽  
Author(s):  
Michael D. Varney ◽  
Krzysztof Appelt ◽  
Vince Kalish ◽  
M. Rami Reddy ◽  
John Tatlock ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Hiv Protease ◽  
Design And Synthesis

Design and synthesis of new enzymes based on the lactate dehydrogenase framework

1991 ◽  
Vol 332 (1263) ◽  
pp. 177-184 ◽  
Keyword(s):  
Crystal Structure ◽  
Lactate Dehydrogenase ◽  
Malate Dehydrogenase ◽  
Functional Groups ◽  
Maximum Rate ◽  
Chemical Probes ◽  
Protein Surface ◽  
Design And Synthesis ◽  
Tryptophan Residues ◽  
Lactate Dehydrogenases

Analysis of the mechanism and structure of lactate dehydrogenases is summarized in a map of the catalytic pathway. Chemical probes, single tryptophan residues inserted at specific sites and a crystal structure reveal slow movements of the protein framework that discriminate between closely related small substrates. Only small and correctly charged substrates allow the protein to engulf the substrate in an internal vacuole that is isolated from solvent protons, in which water is frozen and hydride transfer is rapid. The closed vacuole is very sensitive to the size and charge of the substrate and provides discrimination between small substrates that otherwise have too few functional groups to be distinguished at a solvated protein surface. This model was tested against its ability to successfully predict the design and synthesis of new enzymes such as L-hydroxyisocaproate dehydrogenase and fully active malate dehydrogenase. Solvent friction limits the rate of forming the vacuole and thus the maximum rate of catalysis.

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