7-deazapurine 2 `-deoxyribofuranosides are noncleavable competitive inhibitors of Escherichia coli purine nucleoside phosphorylase (PNP)

DC FieldValueLanguage
dc.contributor.authorBzowska, A
dc.contributor.authorKazimierczuk, Z
dc.contributor.authorSeela, F
dc.date.accessioned2021-12-23T16:10:55Z-
dc.date.available2021-12-23T16:10:55Z-
dc.date.issued1998
dc.identifier.issn0001527X
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/9452-
dc.description.abstractA series of 7-deazapurine 2'-deoxyribofuranosides were synthesized according to already known procedures and their substrate and inhibitor properties with purified E. coli purine nucleoside phosphorylase were examined. In agreement with previous findings, substrate activity was not detected for any of the compounds tested. Most of the nucleosides showed weak inhibition in the preliminary screening, i.e. at a concentration of about 100 mu M. However some combinations of 6-chloro, 6-amino or 6-methoxy substituents with bulky hydrophobic groups at position 7 of the base and/or chloro, amino, methoxy or methylthio group at position 2 markedly enhanced affinity of such modified nucleosides for the E. coli enzyme. The most potent inhibition was observed for two nucleosides: 6-chloro- and 2-amino-6-chloro-7-deazapurine 2'-deoxyribofuranosides that show inhibition constants K-i = 2.4 and 2.3 mu M, respectively. Several other compounds were also found to be good inhibitors, with inhibition constants in the range 5-50 mu M. In all instances the inhibition was competitive us. the nucleoside substrate 7-methylguanosine, Inhibition constants for 7-deazapurine nucleosides are in general several-fold lower than those observed for their purine counterparts. Therefore 7-deaza modification together with substitutions at positions 2, 6 and 7 of the base is a very promising approach to obtain competitive noncleavable inhibitors of E. coli PNP that may bind to the enzyme with inhibition constants in the mu M range.
dc.language.isoen
dc.publisherACTA BIOCHIMICA POLONICA
dc.relation.ispartofACTA BIOCHIMICA POLONICA
dc.subject2'-DEOXYTUBERCIDIN
dc.subject7-deazapurine nucleosides
dc.subjectANALOGS
dc.subjectBiochemistry & Molecular Biology
dc.subjectCATALYTIC MECHANISM
dc.subjectCLADRIBINE
dc.subjectDERIVATIVES
dc.subjectE-coli
dc.subjectGLYCOSYLATION
dc.subjectinhibitors
dc.subjectPHOSPHOROLYSIS
dc.subjectphosphorylase
dc.subjectPURIFICATION
dc.subjectSELECTIVE INHIBITORS
dc.subjectTUBERCIDIN
dc.title7-deazapurine 2 `-deoxyribofuranosides are noncleavable competitive inhibitors of Escherichia coli purine nucleoside phosphorylase (PNP)
dc.typejournal article
dc.identifier.doi10.18388/abp.1998_4269
dc.identifier.isiISI:000076234600016
dc.description.volume45
dc.description.issue3
dc.description.startpage755
dc.description.endpage768
dc.contributor.orcid0000-0002-3976-429X
dc.identifier.eissn1734154X
dc.publisher.placePASTEURA 3, 02-093 WARSAW, POLAND
dcterms.isPartOf.abbreviationActa Biochim. Pol.
dcterms.oaStatusBronze
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