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Titolo:
DISTAMYCIN ANALOGS WITH IMPROVED SEQUENCE-SPECIFIC DNA-BINDING ACTIVITIES
Autore:
CIUCCI A; FERIOTTO G; MISCHIATI C; GAMBARI R; ANIMATI F; LOMBARDI P; NATALI PG; ARCAMONE F; GIACOMINI P;
Indirizzi:
IST REGINA ELENA,IMMUNOL LAB,VIA MESSI ORO 156 I-00158 ROME ITALY IST REGINA ELENA,IMMUNOL LAB I-00158 ROME ITALY MENARINI SUD POMEZIA ITALY UNIV FERRARA,IST CHIM BIOL,CTR INTERDIPARTIMENTALE BIOTECHNOL I-44100FERRARA ITALY
Titolo Testata:
Biochemical pharmacology
fascicolo: 8, volume: 48, anno: 1994,
pagine: 1583 - 1591
SICI:
0006-2952(1994)48:8<1583:DAWISD>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
DR-ALPHA GENE; TRANSCRIPTION; ACTINOMYCIN; NETROPSIN; DODECAMER; ELEMENTS; INHIBIT; OTF-1;
Keywords:
DISTAMYCIN; OCTAMER; HLA-DRA; NUCLEAR FACTORS; ELECTROPHORETIC MOBILITY SHIFT; IN VITRO TRANSCRIPTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
A. Ciucci et al., "DISTAMYCIN ANALOGS WITH IMPROVED SEQUENCE-SPECIFIC DNA-BINDING ACTIVITIES", Biochemical pharmacology, 48(8), 1994, pp. 1583-1591

Abstract

In the present study we have investigated the effect of unprecedentedchemical modifications introduced in the distamycin molecule, with the aim of assessing their ability to interfere with sequence-specific DNA-protein interactions in vitro. By using an electrophoretic mobilityshift assay, we have been able to identify novel distamycin analogueswith improved displacing abilities on the binding of octamer nuclear factors to their target DNA sequence. While variations in the number of pyrrole rings and/or reversion of an internal amide bond result in distamycin-like compounds with identical or very similar properties, the reversion of the formamido into a carboxyamido group or its replacement with the charged formimidoyl moiety significantly improves the ability of the resulting novel distamycin derivatives to complete with OCT-1 (octamer 1 nuclear factor) for its target DNA sequence. tissue-specific octamer-dependent in vitro transcription is similarly affected by these chemical modifications, suggesting that the ability of distamycins to bind octamer sequences has a direct influence on the functional stat of octamer-containing promoters. These data represent an initial, successful attempt to rationalize the design of DNA binding drug, using distamycins as a model.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 00:51:07