Distamycin analogues with improved sequence-specific DNA binding activities

Alessandra Ciucci, Giordana Feriotto, Carlo Mischiati, Roberto Gambari, Fabio Animati, Paolo Lombardi, Pier Giorgio Natali, Federico Arcamone, Patrizio Giacomini

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

In the present study we have investigated the effect of unprecedented chemical modifications introduced in the distamycin molecule, with the aim of assessing their ability to interfere with sequencespecific DNA-protein interactions in vitro. By using an electrophoretic mobility shift assay, we have been able to identify novel distamycin analogues with 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 compete 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 state of octamer-containing promoters. These data represent an initial, successful attempt to rationalize the design of DNA binding drugs, using distamycins as a model.

Original languageEnglish
Pages (from-to)1583-1591
Number of pages9
JournalBiochemical Pharmacology
Volume48
Issue number8
DOIs
Publication statusPublished - Oct 18 1994

Fingerprint

Distamycins
DNA sequences
DNA
Chemical modification
NFI Transcription Factors
Electrophoretic mobility
Pyrroles
Electrophoretic Mobility Shift Assay
Transcription
Amides
Assays
Tissue
Derivatives
Molecules
stallimycin
Pharmaceutical Preparations
Proteins
In Vitro Techniques

Keywords

  • distamycin
  • electrophoretic mobility shift
  • HLA-DRA
  • in vitro transcription
  • nuclear factors
  • octamer

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ciucci, A., Feriotto, G., Mischiati, C., Gambari, R., Animati, F., Lombardi, P., ... Giacomini, P. (1994). Distamycin analogues with improved sequence-specific DNA binding activities. Biochemical Pharmacology, 48(8), 1583-1591. https://doi.org/10.1016/0006-2952(94)90203-8

Distamycin analogues with improved sequence-specific DNA binding activities. / Ciucci, Alessandra; Feriotto, Giordana; Mischiati, Carlo; Gambari, Roberto; Animati, Fabio; Lombardi, Paolo; Giorgio Natali, Pier; Arcamone, Federico; Giacomini, Patrizio.

In: Biochemical Pharmacology, Vol. 48, No. 8, 18.10.1994, p. 1583-1591.

Research output: Contribution to journalArticle

Ciucci, A, Feriotto, G, Mischiati, C, Gambari, R, Animati, F, Lombardi, P, Giorgio Natali, P, Arcamone, F & Giacomini, P 1994, 'Distamycin analogues with improved sequence-specific DNA binding activities', Biochemical Pharmacology, vol. 48, no. 8, pp. 1583-1591. https://doi.org/10.1016/0006-2952(94)90203-8
Ciucci A, Feriotto G, Mischiati C, Gambari R, Animati F, Lombardi P et al. Distamycin analogues with improved sequence-specific DNA binding activities. Biochemical Pharmacology. 1994 Oct 18;48(8):1583-1591. https://doi.org/10.1016/0006-2952(94)90203-8
Ciucci, Alessandra ; Feriotto, Giordana ; Mischiati, Carlo ; Gambari, Roberto ; Animati, Fabio ; Lombardi, Paolo ; Giorgio Natali, Pier ; Arcamone, Federico ; Giacomini, Patrizio. / Distamycin analogues with improved sequence-specific DNA binding activities. In: Biochemical Pharmacology. 1994 ; Vol. 48, No. 8. pp. 1583-1591.
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