We studied the interaction of cis-diammine Pt(II)-bridged bis-netropsin, cis-diammine Pt(II)-bridged bis-distamycin and oligomethylene-bridged bis-netropsin with synthetic DNA fragments containing pseudosymmetrical AT-rich nucleotide sequences and compared it with the interaction of the parent compounds netropsin and distamycin A. For fragments containing multiple blocks of (AIT)4 and (T/A)4 separated by zero, one, two and three GC-base pairs, DNase I footprinting and CD spectroscopy studies reveal that 5'-TTTTAAAA-3' is the strongest affinity binding site for cis-diammine Pt(II)-bridged bis-netropsin and bis-distamycin. They both bind less strongly to a DNA region containing the sequence 5'-AAAATTTT-3'. Netropsin, distamycin A and oligomethylene-bridged bis-netropsin exhibit far less sequence discrimination.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0014-5793(98)01379-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Transcriptional Regulation of Congocidine (Netropsin) Biosynthesis and Resistance.
Appl Environ Microbiol
November 2021
Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France.
The production of specialized metabolites by bacteria is usually temporally regulated. This regulation is complex and frequently involves both global and pathway-specific mechanisms. Streptomyces ambofaciens ATCC23877 produces several specialized metabolites, including spiramycins, stambomycins, kinamycins and congocidine.
View Article and Find Full Text PDFConditional Cooperativity in DNA Minor-Groove Recognition by Oligopeptides.
Molecules
August 2021
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna Pot 113, 1000 Ljubljana, Slovenia.
The recognition of specific DNA sequences in processes such as transcription is associated with a cooperative binding of proteins. Some transcription regulation mechanisms involve additional proteins that can influence the binding cooperativity by acting as corepressors or coactivators. In a conditional cooperativity mechanism, the same protein can induce binding cooperativity at one concentration and inhibit it at another.
View Article and Find Full Text PDFNatural and Synthetic Oligoarylamides: Privileged Structures for Medical Applications.
Chemistry
May 2021
Institut für Organische Chemie und Biomolekulares Wirkstoffzentrum, (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, 30167, Hannover, Germany.
The term "privileged structure" refers to a single molecular substructure or scaffold that can serve as a starting point for high-affinity ligands for more than one receptor type. In this report, a hitherto overlooked group of privileged substructures is addressed, namely aromatic oligoamides, for which there are natural models in the form of cystobactamids, albicidin, distamycin A, netropsin, and others. The aromatic and heteroaromatic core, together with a flexible selection of substituents, form conformationally well-defined scaffolds capable of specifically binding to conformationally well-defined regions of biomacromolecules such as helices in proteins or DNA often by acting as helices mimics themselves.
View Article and Find Full Text PDFNovel distamycin analogues that block the cell cycle of African trypanosomes with high selectivity and potency.
Eur J Med Chem
March 2020
Group Redox Biology of Trypanosomes, Institut Pasteur de Montevideo, Montevideo, Uruguay. Electronic address:
Polyamides-based compounds related to the Streptomycetal distamycin and netropsin are potent cytostatic molecules that bind to AT-rich regions of the minor groove of the DNA, hence interfering with DNA replication and transcription. Recently, derivatives belonging to this scaffold have been reported to halt the proliferation of deadly African trypanosomes by different and unrelated mechanisms. Here we describe the synthesis and preliminary characterization of the anti-trypanosomal mode of action of new potent and selective distamycin analogues.
View Article and Find Full Text PDFCorrecting electrostatic artifacts due to net-charge changes in the calculation of ligand binding free energies.
J Comput Chem
April 2020
Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences, Vienna, Austria.
Alchemically derived free energies are artifacted when the perturbed moiety has a nonzero net charge. The source of the artifacts lies in the effective treatment of the electrostatic interactions within and between the perturbed atoms and remaining (partial) charges in the simulated system. To treat the electrostatic interactions effectively, lattice-summation (LS) methods or cutoff schemes in combination with a reaction-field contribution are usually employed.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!