Plasmodium falciparum G-quadruplex DNA (PfG4)

Plasmodium falciparum G-quadruplex (PfG4) DNA sequences are non-canonical secondary structures formed by guanine-rich regions within the genome of the primary malaria-causing parasite (Harris et al., 2018, Nucleic Acids Research). These structures consist of stacked G-tetrads stabilized by Hoogsteen hydrogen bonding and monovalent cations. In P. falciparum, G4s are significantly enriched in key regulatory regions, including telomeres and the promoter regions of var genes, which are responsible for antigenic variation and immune evasion (Marsico et al., 2019, Scientific Reports). By acting as physical barriers or regulatory nodes, PfG4s influence essential processes such as DNA replication, transcription, and telomere stability (Calvo & Wasserman, 2016, Memórias do Instituto Oswaldo Cruz). Targeting these structures with small-molecule ligands, known as G4 stabilizers, offers a novel therapeutic strategy to disrupt the parasite's life cycle and overcome drug resistance (Belmonte-Reche et al., 2016, Future Medicinal Chemistry). Such ligands can inhibit telomerase activity or cause genomic instability by blocking polymerase progression, leading to potent anti-plasmodial effects. Consequently, PfG4s represent a promising target for developing next-generation antimalarial drugs that may bypass existing resistance mechanisms.

Other names

Plasmodium falciparum G4 DNAP. falciparum G-quadruplexesG-quadruplex DNA sequences in Plasmodium falciparumPfG4-DNA

Stabilization of G-quadruplex structures to inhibit DNA replication, transcription, and telomere maintenance, thereby inducing parasite cell death.