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Titolo:
NMR EVIDENCE OF SEQUENCE-SPECIFIC DNA-BINDING BY A COBALT(III)-BLEOMYCIN ANALOG WITH TETHERED ACRIDINE
Autore:
TAN JD; FARINAS ET; DAVID SS; MASCHARAK PK;
Indirizzi:
UNIV CALIF SANTA CRUZ,DEPT CHEM & BIOCHEM SANTA CRUZ CA 95064 UNIV CALIF SANTA CRUZ,DEPT CHEM & BIOCHEM SANTA CRUZ CA 95064
Titolo Testata:
Inorganic chemistry
fascicolo: 19, volume: 33, anno: 1994,
pagine: 4295 - 4308
SICI:
0020-1669(1994)33:19<4295:NEOSDB>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
NUCLEAR MAGNETIC-RESONANCE; DECADEOXYRIBONUCLEOTIDE D-)CGCAATTGCG>2; DEOXYRIBONUCLEIC-ACID; THIAZOLE-LEXITROPSIN; COBALT BLEOMYCIN; BASE SPECIFICITY; METAL-COMPLEXES; INTERCALATION; H-1-NMR; RECOGNITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
48
Recensione:
Indirizzi per estratti:
Citazione:
J.D. Tan et al., "NMR EVIDENCE OF SEQUENCE-SPECIFIC DNA-BINDING BY A COBALT(III)-BLEOMYCIN ANALOG WITH TETHERED ACRIDINE", Inorganic chemistry, 33(19), 1994, pp. 4295-4308

Abstract

Attachment of acridine-9-carboxamido-N'-(3-propyl)imidazole (8, Int-A) to the Co(III) complex of a designed ligand PMAH that mimics the metal-binding domain of the antitumor drug bleomycin (BLM) has afforded the hybrid molecule [Co(PMA)(Int-A)]Cl-2 (7). This structurally characterized compound inflicts DNA strand scission under UV light much like the Co(m)-BLMs. It has been shown previously that UV irradiation of the [Co-(PMA)](2+) unit gives rise to a ligand-based radical which, in aqueous medium, rapidly collapses into (OH)-O-. radical, the species actually responsible for the DNA photocleavage observed with the [Co(PMA)X](n+) complexes. In this paper we report that attachment of the intercalator acridine to the DNA-cleaving [Co(PMA)](2+) unit not only allows the resulting hybrid molecule 7 to bind to DNA quite strongly but also results in preferential DNA photocleavage at 5'GG-N3' sites. Specific interactions between 7 and the DNA substrate have been studied by high-field NOESY and COSY experiments using the self-complimentary oligonucleotide [d(GATCCGGATC)](2) (9) which contains a GG-N site. Intercalative interaction between the acridine moiety of 7 and the duplex 9 is indicated by both broadening and upfield shifts of the acridine protons in the 7-9 (1:1) complex. Specific NOEs between the nonexchangeable base protons and the sugar protons of 9 also demonstrate that the acridine moiety of 7 intercalates into the G-G step of 9 and does so (a) with only the outer half (the N-containing side) of the acridine moiety within the base pairs and (b) from the major groove side of the duplex. Interestingly, no intermolecular NOE between the protons of the [Co(PMA)](2+) unit of 7 and those of 9 is observed in the NOESY spectra of the 7-9 (1:1) complex. Also, the resonances of the [Co(PMA)](2+) unit are strongly affected by the salt concentration. The latter two observations indicate that the [Co(PMA)](2+) unit of 7 binds to the phosphate backbone of 9 via electrostatic interaction. The products of photocleavage of radiolabeled 9 with 7 suggest that the acridine moiety of 7 binds to the G-G site of 9 and allows photodamage at the GGN sites by the tethered [Co(PMA)](2+) unit.

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Documento generato il 25/09/20 alle ore 07:44:02