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Titolo:
A NEW CLASS OF ARTIFICIAL NUCLEASES THAT RECOGNIZE AND CLEAVE APURINIC SITES IN DNA WITH GREAT SELECTIVITY AND EFFICIENCY
Autore:
FKYERAT A; DEMEUNYNCK M; CONSTANT JF; MICHON P; LHOMME J;
Indirizzi:
UNIV JOSEPH FOURIER,LEDSS,CNRS,URA 332,BP 53X F-38041 GRENOBLE FRANCE UNIV JOSEPH FOURIER,LEDSS,CNRS,URA 332,BP 53X F-38041 GRENOBLE FRANCE
Titolo Testata:
Journal of the American Chemical Society
fascicolo: 22, volume: 115, anno: 1993,
pagine: 9952 - 9959
SICI:
0002-7863(1993)115:22<9952:ANCOAN>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
COLI ENDONUCLEASE-III; ESCHERICHIA-COLI; APYRIMIDINIC SITES; ABASIC SITES; DEOXYRIBONUCLEIC-ACID; REPAIR ENZYMES; MUTAGENESIS; DEPURINATION; MOLECULES; MECHANISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
45
Recensione:
Indirizzi per estratti:
Citazione:
A. Fkyerat et al., "A NEW CLASS OF ARTIFICIAL NUCLEASES THAT RECOGNIZE AND CLEAVE APURINIC SITES IN DNA WITH GREAT SELECTIVITY AND EFFICIENCY", Journal of the American Chemical Society, 115(22), 1993, pp. 9952-9959

Abstract

A series of tailor-made molecules, 1 and 4-7, have been prepared to recognize and cleave DNA at apurinic sites. These molecules incorporatein their structure different units designed for specific functions: (1) an intercalator for DNA binding, (2) a nucleic base for abasic siterecognition, and (3) a linker endowed with both a binding function and a cleavage function (Scheme II). The constituent units were varied successively in the series of molecules to get insight into their mode of action and prepare more active compounds. H-1 NMR spectroscopy reveals the absence of intramolecular ring-ring stacking interactions in water between the base and the intercalator in all molecules 1 and 4-7. All bind to calf thymus DNA with binding constants ranging from 10(4)to 10(6) M-1. Their nuclease activity was estimated by measuring their ability to induce single strand breaks in depurinated pBR 322 plasmid DNA. The most efficient molecule, 5, exhibits high recognition selectivity and cleavage efficiency: at nanomolar concentrations, 5 recognizes and cleaves the abasic lesion present in a DNA molecule containingan average of 1.8 apurinic sites in its 4 362 base pairs sequence. Molecule 5 exhibits higher cleaving efficiency than the reported tripeptide Lys-Trp-Lys: 10(-8) M concentrations of the former (5) lead to cleavage ratios comparable to those observed for the latter used as 10(-3) M concentration. This enzyme mimic 5 can be used advantageously as asubstitute to the natural nuclease for in vitro cleavage of depurinated DNA.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 08:06:37