The DNA complexes with distactins have been investigated by means of spectrophotometry, viscosimetry and flow birefringence methods. The distactins are actinocin's derivatives containing in the 1,9 positions of the phenoxazone moiety oligopyrrolcarboxamide groups (like those of distamycin A), which have from one to three fragments of 1-methyl-4-amino-2-pyrrolic acid. The mode of DNA-distactins binding in water solution depends on the quantity of the methylpyrrole rings in the oligopeptide groups. The ligand with oligopeptide groups containing three methylpyrrole rings joins the DNA double helix only from outside by means of oligopeptide groups. The compounds with one and two methylpyrrole rings form two kinds of complexes with DNA: external binding and intercalation. In the latter case both chromophore and methylpyrrole fragments, interact with DNA.
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Mini Rev Med Chem
January 2019
Department of Organic Chemistry, Medical University, Bialystok 15-222, Mickiewicza Street 2c, Poland.
The DNA as the depository of genetic information is a natural target for chemotherapy. A lot of anticancer and antimicrobial agents derive their biological activity from their selective interaction with DNA in the minor groove and from their ability to interfere with biological processes such as enzyme catalysis, replication and transcription. The discovery of the details of minor groove binding drugs, such as netropsin and distamycin A, oligoamides built of 4-amino-1-methylpyrrole-2-carboxylic acid residues, allowed to develop various DNA sequence-reading molecules, named lexitropsins, capable of interacting with DNA precisely, strongly and with a high specificity, and at the same time exhibiting significant cytotoxic potential.
View Article and Find Full Text PDFChemistry
August 2018
Department of Chemistry, Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka, 558-8585, Japan.
Nitronyl nitroxide (NN)-substituted conjugated oligomers, which were expected to self-associate in biradical cation states, were designed to analyze the capability of π-dimers as molecular wires. The oligomer moieties were composed of dithienyl-N-methylpyrrole with methoxy substituents at the inner β-position of thiophene rings (DTP-NN ) and its propylenedioxythiophene (ProDOT) inserted derivative (DTP-P-NN ), or two ethylenedioxythiophene (EDOT) and two ProDOT units (E P -NN ). Among them, chemical one-electron oxidation gave biradical cations (DTP-P) -NN and (E P ) -NN that formed π-dimers (DTP-P-NN ) and (E P -NN ) in dichloromethane at low temperatures.
View Article and Find Full Text PDFBioorg Med Chem
August 2016
Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawaoiwakecho, Sakyo, Kyoto 606-8502, Japan; Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Yoshida-Ushinomiyacho, Sakyo, Kyoto 606-8501, Japan. Electronic address:
With the aim of improving aqueous solubility, we designed and synthesized five N-methylpyrrole (Py)-N-methylimidazole (Im) polyamides capable of recognizing 9-bp sequences. Their DNA-binding affinities and sequence specificities were evaluated by SPR and Bind-n-Seq analyses. The design of polyamide 1 was based on a conventional model, with three consecutive Py or Im rings separated by a β-alanine to match the curvature and twist of long DNA helices.
View Article and Find Full Text PDFCurr Top Med Chem
August 2016
Department of Chemistry, National Sun Yat Sen University, Kaohsiung, Taiwan.
Distamycin and netropsin analogues have been designed for targeting specific sequences in DNA. Numerous reviews have been centered on the replacement of N-methylpyrrole with heteroaromatic rings in order to induce better fitting to improve the binding efficiency and the introduction of additional interactions for recognition of GC base pairs at the minor groove of DNA. Most of these designed analogs retained the use of carboxamide-bond for interconnecting the heteroaromatic rings.
View Article and Find Full Text PDFJ Org Chem
September 2013
Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
A series of 2,5-di(2-thienyl)-N-methylpyrrole derivatives 1a-1d with methylthio end-capping groups and electron-donating substituents at the 3-position of the thiophene rings was synthesized, and the effects of the substituents on the structure, stability, and π-dimerization ability of the radical cation were investigated using UV-vis-NIR and electron spin resonance spectra and density functional theory (DFT) calculations. Among the electron-donating methyl, methoxy, and methylthio substituents, the methoxy derivative 1c gave the most stable radical cation, which persisted in dichloromethane at room temperature under nitrogen for several hours without any apparent decomposition. In addition, 1c(•+) had the largest π-dimerization enthalpy among 1a(•+)-1d(•+).
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