FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2002253224> ?p ?o ?g. }

• W2002253224 endingPage "1617" @default.
• W2002253224 startingPage "1607" @default.
• W2002253224 abstract "Thymidylate synthase is an attractive target for antiproliferative drug design because of its key role in the synthesis of DNA. As such, the enzyme has been widely targeted for anticancer applications. In principle, TS should also be a good target for drugs used to fight infectious disease. In practice, TS is highly conserved across species, and it has proven to be difficult to develop inhibitors that are selective for microbial TS enzymes over the human enzyme. Using the structure of TS from Lactobacillus casei in complex with the nonsubstrate analogue phenolphthalein, inhibitors were designed to take advantage of features of the bacterial enzyme that differ from those of the human enzyme. Upon synthesis and testing, these inhibitors were found to be up to 40-fold selective for the bacterial enzyme over the human enzyme. The crystal structures of two of these inhibitors in complex with TS suggested the design of further compounds. Subsequent synthesis and testing showed that these second-round compounds inhibit the bacterial enzyme at sub-micromolar concentrations, while the human enzyme was not inhibited at detectable levels (selectivities of 100−1000-fold or greater). Although these inhibitors share chemical similarities, X-ray crystal structures reveal that the analogues bind to the enzyme in substantially different orientations. Site-directed mutagenesis experiments suggest that the individual inhibitors may adopt multiple configurations in their complexes with TS." @default.
• W2002253224 created "2016-06-24" @default.
• W2002253224 creator A5009419179 @default.
• W2002253224 creator A5011428136 @default.
• W2002253224 creator A5017739633 @default.
• W2002253224 creator A5050306209 @default.
• W2002253224 creator A5053651486 @default.
• W2002253224 creator A5058934270 @default.
• W2002253224 creator A5059465522 @default.
• W2002253224 creator A5067042371 @default.
• W2002253224 creator A5079322760 @default.
• W2002253224 creator A5082478496 @default.
• W2002253224 date "1999-01-13" @default.
• W2002253224 modified "2023-10-07" @default.
• W2002253224 title "Structure-Based Design of Inhibitors Specific for Bacterial Thymidylate Synthase^," @default.
• W2002253224 cites W1498566120 @default.
• W2002253224 cites W1508681581 @default.
• W2002253224 cites W1742102714 @default.
• W2002253224 cites W1975773321 @default.
• W2002253224 cites W1983638771 @default.
• W2002253224 cites W1986191025 @default.
• W2002253224 cites W1993353893 @default.
• W2002253224 cites W2013936203 @default.
• W2002253224 cites W2046441811 @default.
• W2002253224 cites W2053963992 @default.
• W2002253224 cites W2074713052 @default.
• W2002253224 cites W2081532044 @default.
• W2002253224 cites W2085445720 @default.
• W2002253224 cites W2086863971 @default.
• W2002253224 cites W2161117347 @default.
• W2002253224 cites W2176123637 @default.
• W2002253224 cites W2949679049 @default.
• W2002253224 cites W4239840825 @default.
• W2002253224 cites W4250943815 @default.
• W2002253224 doi "https://doi.org/10.1021/bi9815896" @default.
• W2002253224 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9931028" @default.
• W2002253224 hasPublicationYear "1999" @default.
• W2002253224 type Work @default.
• W2002253224 sameAs 2002253224 @default.
• W2002253224 citedByCount "48" @default.
• W2002253224 countsByYear W20022532242012 @default.
• W2002253224 countsByYear W20022532242013 @default.
• W2002253224 countsByYear W20022532242016 @default.
• W2002253224 countsByYear W20022532242017 @default.
• W2002253224 countsByYear W20022532242020 @default.
• W2002253224 crossrefType "journal-article" @default.
• W2002253224 hasAuthorship W2002253224A5009419179 @default.
• W2002253224 hasAuthorship W2002253224A5011428136 @default.
• W2002253224 hasAuthorship W2002253224A5017739633 @default.
• W2002253224 hasAuthorship W2002253224A5050306209 @default.
• W2002253224 hasAuthorship W2002253224A5053651486 @default.
• W2002253224 hasAuthorship W2002253224A5058934270 @default.
• W2002253224 hasAuthorship W2002253224A5059465522 @default.
• W2002253224 hasAuthorship W2002253224A5067042371 @default.
• W2002253224 hasAuthorship W2002253224A5079322760 @default.
• W2002253224 hasAuthorship W2002253224A5082478496 @default.
• W2002253224 hasConcept C100544194 @default.
• W2002253224 hasConcept C104317684 @default.
• W2002253224 hasConcept C123321153 @default.
• W2002253224 hasConcept C16318435 @default.
• W2002253224 hasConcept C181199279 @default.
• W2002253224 hasConcept C185592680 @default.
• W2002253224 hasConcept C2776662696 @default.
• W2002253224 hasConcept C2776694085 @default.
• W2002253224 hasConcept C2780456651 @default.
• W2002253224 hasConcept C501734568 @default.
• W2002253224 hasConcept C54355233 @default.
• W2002253224 hasConcept C55493867 @default.
• W2002253224 hasConcept C71240020 @default.
• W2002253224 hasConcept C86803240 @default.
• W2002253224 hasConceptScore W2002253224C100544194 @default.
• W2002253224 hasConceptScore W2002253224C104317684 @default.
• W2002253224 hasConceptScore W2002253224C123321153 @default.
• W2002253224 hasConceptScore W2002253224C16318435 @default.
• W2002253224 hasConceptScore W2002253224C181199279 @default.
• W2002253224 hasConceptScore W2002253224C185592680 @default.
• W2002253224 hasConceptScore W2002253224C2776662696 @default.
• W2002253224 hasConceptScore W2002253224C2776694085 @default.
• W2002253224 hasConceptScore W2002253224C2780456651 @default.
• W2002253224 hasConceptScore W2002253224C501734568 @default.
• W2002253224 hasConceptScore W2002253224C54355233 @default.
• W2002253224 hasConceptScore W2002253224C55493867 @default.
• W2002253224 hasConceptScore W2002253224C71240020 @default.
• W2002253224 hasConceptScore W2002253224C86803240 @default.
• W2002253224 hasIssue "5" @default.
• W2002253224 hasLocation W20022532241 @default.
• W2002253224 hasLocation W20022532242 @default.
• W2002253224 hasOpenAccess W2002253224 @default.
• W2002253224 hasPrimaryLocation W20022532241 @default.
• W2002253224 hasRelatedWork W1984994946 @default.
• W2002253224 hasRelatedWork W1993875123 @default.
• W2002253224 hasRelatedWork W2010366112 @default.
• W2002253224 hasRelatedWork W2048029409 @default.
• W2002253224 hasRelatedWork W2077723644 @default.
• W2002253224 hasRelatedWork W2153582959 @default.
• W2002253224 hasRelatedWork W2392930094 @default.
• W2002253224 hasRelatedWork W3031205269 @default.
• W2002253224 hasRelatedWork W3126194493 @default.

• next