Cart
Article
Structure−Activity Relationships for a Class of Inhibitors of Purine Nucleoside Phosphorylase
Full Text HTML
Hi-Res PDFPurchase the full-text
- PDF/HTML,
figures/images,
references and tables,
(where available)
Section:Abstract
Values of inhibition constants, Ki, for a family of structurally related, competitive inhibitors of calf spleen purine nucleoside phosphorylase (PNP) have been determined employing both inosine as substrate and a manual assay and 2-amino-6-mercapto-7-methylpurine ribonucleoside (MESG) as substrate and a robot-based enzyme kinetics facility. Several of the values determined robotically were confirmed employing the same substrate and a manual assay. Surprisingly, for many of the inhibitors examined, values of Ki determined with MESG as substrate are smaller than those obtained employing inosine as substrate by a factor that varies from less than 2 to 10. Values of concentrations required for 50% inhibition of PNP, IC50, have also been determined for the same family of inhibitors employing inosine as substrate. Values of IC50ino and those for Kiino and Kimesg for subsets of the inhibitors have been employed as training sets to create quantitative structure−activity relationships (QSAR) which have substantial power to predict values of IC50 and Ki for inhibitors outside the training set. These QSAR models should be useful in guiding future medicinal chemistry efforts designed to discover inhibitors of PNP having increased potency.
Citing Articles
Citation data is made available by participants in CrossRef's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search in SciFinder.
This article has been cited by 4 ACS Journal articles (4 most recent appear below).
Discovery of New Inhibitors of Schistosoma mansoni PNP by Pharmacophore-Based Virtual Screening
Matheus P. Postigo, Rafael V. C. Guido, Glaucius Oliva, Marcelo S. Castilho, Ivan da R. Pitta, Julianna F. C. de Albuquerque, and Adriano D. AndricopuloJournal of Chemical Information and Modeling2010 50 (9), 1693-1705Discovery of New Inhibitors of Schistosoma mansoni PNP by Pharmacophore-Based Virtual Screening
Matheus P. Postigo, Rafael V. C. Guido, Glaucius Oliva, Marcelo S. Castilho, Ivan da R. Pitta, Julianna F. C. de Albuquerque, and Adriano D. AndricopuloJournal of Chemical Information and Modeling2010 50 (9), 1693-1705Schistosomiasis is considered the second most important tropical parasitic disease, with severe socioeconomic consequences for millions of people worldwide. Schistosoma mansoni, one of the causative agents of human schistosomiasis, is unable to synthesize ...
Structural Basis for Selective Inhibition of Trypanosomatid Glyceraldehyde-3-Phosphate Dehydrogenase: Molecular Docking and 3D QSAR Studies
Rafael V. C. Guido, Glaucius Oliva, Carlos A. Montanari and Adriano D. AndricopuloJournal of Chemical Information and Modeling2008 48 (4), 918-929Structural Basis for Selective Inhibition of Trypanosomatid Glyceraldehyde-3-Phosphate Dehydrogenase: Molecular Docking and 3D QSAR Studies
Rafael V. C. Guido, Glaucius Oliva, Carlos A. Montanari and Adriano D. AndricopuloJournal of Chemical Information and Modeling2008 48 (4), 918-929The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is as an attractive target for the development of novel antitrypanosomatid agents. In the present work, comparative molecular field analysis and comparative molecular similarity index ...
Information Decay in Molecular Docking Screens against Holo, Apo, and Modeled Conformations of Enzymes
Susan L. McGovern and Brian K. ShoichetJournal of Medicinal Chemistry2003 46 (14), 2895-2907Information Decay in Molecular Docking Screens against Holo, Apo, and Modeled Conformations of Enzymes
Susan L. McGovern and Brian K. ShoichetJournal of Medicinal Chemistry2003 46 (14), 2895-2907Molecular docking uses the three-dimensional structure of a receptor to screen a small molecule database for potential ligands. The dependence of docking screens on the conformation of the binding site remains an open question. To evaluate the information ...
Stochastic Similarity Selections from Large Combinatorial Libraries
Victor S. Lobanov and Dimitris K. AgrafiotisJournal of Chemical Information and Computer Sciences2000 40 (2), 460-470Stochastic Similarity Selections from Large Combinatorial Libraries
Victor S. Lobanov and Dimitris K. AgrafiotisJournal of Chemical Information and Computer Sciences2000 40 (2), 460-470A stochastic procedure for similarity searching in large virtual combinatorial libraries is presented. The method avoids explicit enumeration and calculation of descriptors for every virtual compound, yet provides an optimal or nearly optimal similarity ...
Tools
-
Add to Favorites
-
Download Citation
-
Email a Colleague -
Permalink
Order Reprints
Rights & Permissions
Citation Alerts
History
- Published In Issue July 01, 1999
- Received January 22, 1999
ACS
Network
Facebook
Tweet This
CiteULike
Newsvine
Digg This
Delicious
