G-Quadruplex DNA Motifs in the Malaria Parasite Plasmodium falciparum and Their Potential as Novel Antimalarial Drug Targets

• DOI: 10.1128/aac.01828-17
• Publication Date: 2018-01-08T12:05:15Z
• Authors: Lynne M. Harris; Katelyn R. Monsell; Florian Noulin; M. Toyin Famodimu; Nicolas Smargiasso; Christian Damblon; Paul Horrocks; Catherine J. Merrick
• Keywords: G-quadruplex; Transcription; Alu element

ABSTRACT G-quadruplexes are DNA or RNA secondary structures that can be formed from guanine-rich nucleic acids. These four-stranded structures, composed of stacked quartets guanine bases, highly stable and have been demonstrated to occur in vivo the human cells other systems, where they play important biological roles, influencing processes such as telomere maintenance, replication transcription, or, case G-quadruplexes, translation processing. We report for first time detected nuclei malaria parasite Plasmodium falciparum , which has one most A/T-biased genomes sequenced therefore possesses few sequences with potential form G-quadruplexes. show despite this paucity putative G-quadruplex-forming sequences, P. parasites sensitive several G-quadruplex-stabilizing drugs, including quarfloxin, previously reached phase 2 clinical trials an anticancer drug. Quarfloxin a rapid initial rate kill is active against ring stages well replicative intraerythrocytic development. suppress transcription G-quadruplex-containing reporter gene but quarfloxin does not appear disrupt rRNAs, was proposed its mode action both trypanosomes. data suggest repositioning antimalarial novel action. Furthermore, G-quadruplex biology may present target development new drugs.