Artificial molecules that mimic DNA
I. Huc, JM Schmitter (CBMN), S. Chaignepain (IBGC, CBMN), P. Pourquier (INSERM, CRCM, U. Montpellier), V. Parissi (CNRS, MFP)
New DNA mimic foldamers with potential therapeutical purposes
Numerous essential biomolecular processes require the recognition of DNA surface features by proteins. Molecules mimicking these features could potentially act as decoys and interfere with pharmacologically or therapeutically relevant protein-DNA interactions. Although naturally occurring DNA-mimicking proteins have been described, synthetic tunable molecules that mimic the charge surface of double-stranded DNA are not known. Researchers at the Institut de Chimie et Biologie des Membranes et Nano-objets (Pr I. Huc, Pr JM Schmitter, Dr S. Chaignepain, CBMN, CNRS/Bordeaux University/Bordeaux INP), the Laboratoire de Microbiologie Fondamentale et Pathogénicité (Dr V. Parissi, MFP, CNRS/Bordeaux University) and the Institut de Recherche en Cancérologie de Montpellier (Dr P. Pourquier, Inserm/Montpellier University) have successfully synthesized helical molecules that precisely imitate the surface features of DNA double helix and proved their inhibitory effects on two therapeutical targets: the topoisomerase 1 and the HIV-1 integrase. These aromatic oligoamides fold into single helical conformations and display a double helical array of negatively charged residues in positions that match the phosphate moieties in B-DNA. The molecules were able to inhibit several enzymes possessing non-sequence-selective DNA-binding properties, including topoisomerase 1 and HIV-1 integrase, presumably through specific foldamer-protein interactions. Such modular and synthetically accessible DNA mimics provide a versatile platform to design novel inhibitors of protein-DNA interactions as well as new tools for investigating the molecular processes underlying the protein-DNA interactions.
Single helically folded aromatic oligoamides that mimic the charge surface of double-stranded B-DNA. Krzysztof Ziach, Céline Chollet, Vincent Parissi, Panchami Prabhakaran, Mathieu Marchivie, Valentina Corvaglia, Partha Pratim Bose, Katta Laxmi-Reddy, Frédéric Godde, Jean-Marie Schmitter, Stéphane Chaignepain, Philippe Pourquier, and Ivan Huc. Nature Chemistry, April 2, 2018. DOI: http://dx.doi.org/10.1038/s41557-018-0018-7