Gemcitabine, Pyrrologemcitabine, and 2 `-Fluoro-2 `-Deoxycytidines: Synthesis, Physical Properties, and Impact of Sugar Fluorination on Silver Ion Mediated Base Pairing

DC FieldValueLanguage
dc.contributor.authorGuo, Xiurong
dc.contributor.authorLeonard, Peter
dc.contributor.authorIngale, Sachin A.
dc.contributor.authorSeela, Frank
dc.date.accessioned2021-12-23T16:06:39Z-
dc.date.available2021-12-23T16:06:39Z-
dc.date.issued2017
dc.identifier.issn09476539
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/7498-
dc.description.abstractThe stability of silver-mediated ``dC-dC'' base pairs relies not only on the structure of the nucleobase, but is also sensitive to structural modification of the sugar moiety. 2'-Fluorinated 2'-deoxycytidines with fluorine atoms in the arabino (up) and ribo (down) configuration as well as with geminal fluorine substitution (anticancer drug gemcitabine) and the novel fluorescent phenylpyrrolo-gemcitabine ((ph)PyrGem) have been synthesized. All the nucleosides display the recognition face of naturally occurring 2'-deoxycytidine. The nucleosides were converted into phosphoramidites and incorporated into 12-mer oligonucleotides by solid-phase synthesis. The addition of silver ions to DNA duplexes with a fluorine-modified ``dC-dC'' pair near the central position led to significant duplex stabilization. The increase in stability was higher for duplexes with fluorinated sugar residues than for those with an unchanged 2 `-deoxyribose moiety. Similar observations were made for ``dC-dT'' pairs and to a minor extent for ``dC-dA'' pairs. The increase in silver ion mediated base-pair stability was reversed by annulation of a pyrrole ring to the cytosine moiety, as shown for 2 `-fluorinated (ph)PyrGem in comparison with phenylpyrrolo-dC ((ph)PyrdC). This phenomenon results from stereoelectronic effects induced by fluoro substitution, which are transmitted from the sugar moiety to the silver ion mediated base pairs. The extent of the effect depends on the number of fluorine substituents, their configuration, and the structure of the nucleobase.
dc.description.sponsorshipChemBioTech, Munster, Germany; The authors thank Miss Oxana Korshenko for the oligonucleotide syntheses, Dr. Letzel, Organisch-Chemisches Institut, Universitat Munster, Germany, for the measurement of the MALDI mass spectra, and Prof. Dr. B. Wunsch, Institut fur Pharmazeutische und Medizinische Chemie, Universitat Munster, Germany, for providing 400 and 600 MHz NMR spectra. Financial support by ChemBioTech, Munster, Germany, is gratefully acknowledged.
dc.language.isoen
dc.publisherWILEY-V C H VERLAG GMBH
dc.relation.ispartofCHEMISTRY-A EUROPEAN JOURNAL
dc.subjectAG+ IONS
dc.subjectbase pairing
dc.subjectBINDING
dc.subjectChemistry
dc.subjectChemistry, Multidisciplinary
dc.subjectDNA
dc.subjectDNA DUPLEXES
dc.subjectduplex stability
dc.subjectfluorine
dc.subjectMETAL-IONS
dc.subjectNUCLEOSIDES
dc.subjectOLIGONUCLEOTIDES
dc.subjectPARALLEL
dc.subjectPYRROLO-DC
dc.subjectRNA
dc.subjectsilver
dc.subjectSTABILITY
dc.titleGemcitabine, Pyrrologemcitabine, and 2 `-Fluoro-2 `-Deoxycytidines: Synthesis, Physical Properties, and Impact of Sugar Fluorination on Silver Ion Mediated Base Pairing
dc.typejournal article
dc.identifier.doi10.1002/chem.201703427
dc.identifier.isiISI:000418075600019
dc.description.volume23
dc.description.issue70
dc.description.startpage17740
dc.description.endpage17754
dc.identifier.eissn15213765
dc.publisher.placePOSTFACH 101161, 69451 WEINHEIM, GERMANY
dcterms.isPartOf.abbreviationChem.-Eur. J.
Show simple item record

Page view(s)

2
Last Week
0
Last month
0
checked on Apr 21, 2024

Google ScholarTM

Check

Altmetric