DC Field | Value | Language |
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dc.contributor.author | Knockaert, M | - |
dc.contributor.author | Gray, N | - |
dc.contributor.author | Damiens, E | - |
dc.contributor.author | Chang, Young-Tae | - |
dc.contributor.author | Grellier, P | - |
dc.contributor.author | Grant, K | - |
dc.contributor.author | Fergusson, D | - |
dc.contributor.author | Mottram, J | - |
dc.contributor.author | Soete, M | - |
dc.contributor.author | Dubremetz, JF | - |
dc.contributor.author | Le Roch, K | - |
dc.contributor.author | Doerig, C | - |
dc.contributor.author | Schultz, PG | - |
dc.contributor.author | Meijer, L | - |
dc.date.accessioned | 2018-06-15T05:09:15Z | - |
dc.date.available | 2018-06-15T05:09:15Z | - |
dc.date.created | 2017-09-08 | - |
dc.date.issued | 2000-06 | - |
dc.identifier.issn | 1074-5521 | - |
dc.identifier.uri | https://oasis.postech.ac.kr/handle/2014.oak/50144 | - |
dc.description.abstract | Background: Chemical inhibitors of cyclin-dependent kinases (CDKs) have great therapeutic potential against various proliferative and neurodegenerative disorders. Olomoucine, a 2,6,9-trisubstituted purine, has been optimized for activity against CDK1/cyclin B by combinatorial and medicinal chemistry efforts to yield the purvalanol inhibitors. Although many studies support the action of purvalanols against CDKs, the actual intracellular targets of 2,6,9-trisubstituted purines remain unverified. Results: To address this issue, purvalanol B (95) and an NG-methylated, CDK-inactive derivative (95M) were immobilized on an agarose matrix. Extracts from a diverse collection of cell types and organisms were screened for proteins binding purvalanol B. In addition to validating CDKs as intracellular targets, a variety of unexpected protein kinases were recovered from the 95 matrix. Casein kinase 1 (CK1) was identified as a principal 95 matrix binding protein in Plasmodium falciparum, Leishmania mexicana, Toxoplasma gondii and Trypanosoma cruzi. Purvalanol compounds also inhibit the proliferation of these parasites, suggesting that CK1 is a valuable target for further screening with 2,6,9-trisubstituted purine libraries. Conclusions: That a simple batchwise affinity chromatography approach using two purine derivatives facilitated isolation of a small set of highly purified kinases suggests that this could be a general method for identifying intracellular targets relevant to a particular Glass of ligands. This method allows a close correlation to be established between the pattern of proteins bound to a small family of related compounds and the pattern of cellular responses to these compounds. | - |
dc.language | English | - |
dc.publisher | CURRENT BIOLOGY LTD | - |
dc.relation.isPartOf | CHEMISTRY & BIOLOGY | - |
dc.title | Intracellular targets of cyclin-dependent kinase inhibitors: identification by affinity chromatography using immobilised inhibitors | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/S1074-5521(00)00124-1 | - |
dc.type.rims | ART | - |
dc.identifier.bibliographicCitation | CHEMISTRY & BIOLOGY, v.7, no.6, pp.411 - 422 | - |
dc.identifier.wosid | 000087683100007 | - |
dc.citation.endPage | 422 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 411 | - |
dc.citation.title | CHEMISTRY & BIOLOGY | - |
dc.citation.volume | 7 | - |
dc.contributor.affiliatedAuthor | Chang, Young-Tae | - |
dc.identifier.scopusid | 2-s2.0-0034086397 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.type.docType | Article | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
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