Facile room-temperature self-assembly of extended cation-free guanine-quartet network on Mo-doped Au(111) surface

Guanine-quadruplex, consisting of several stacked guanine-quartets (GQs), has emerged as an important category of novel molecular targets with applications from nanoelectronic devices to anticancer drugs. Incorporation of metal cations into...

The significance of the metal cation in guanine-quartet – metalloporphyrin complexes

The distinct positions of the divalent metal ions with respect to the porphyrin ring are responsible for different interaction energies between metalloporphyrins and the guanine quartet.

Discovery of G-quadruplex-forming sequences in SARS-CoV-2

The outbreak caused by the novel coronavirus SARS-CoV-2 has been declared a global health emergency. G-quadruplex structures in genomes have long been considered essential for regulating a number of biological processes in a plethora of organisms. We have analyzed and identified 25 four contiguous GG runs (G2NxG2NyG2NzG2) in the SARS-CoV-2 RNA genome, suggesting putative G-quadruplex-forming sequences (PQSs). Detailed analysis of SARS-CoV-2 PQSs revealed their locations in the open reading frames of ORF1 ab, spike (S), ORF3a, membrane (M) and nucleocapsid (N) genes. Identical PQSs were also found in the other members of the Coronaviridae family. The top-ranked PQSs at positions 13385 and 24268 were confirmed to form RNA G-quadruplex structures in vitro by multiple spectroscopic assays. Furthermore, their direct interactions with viral helicase (nsp13) were determined by microscale thermophoresis. Molecular docking model suggests that nsp13 distorts the G-quadruplex structure by allowing the guanine bases to be flipped away from the guanine quartet planes. Targeting viral helicase and G-quadruplex structure represents an attractive approach for potentially inhibiting the SARS-CoV-2 virus.

Properties of the excited electronic states of guanine quartet complexes with alkali metal cations

G-quartets are supra-molecular structures that consist of four guanine molecules connected by eight hydrogen bonds. They are additionally stabilized by metal cations. In this contribution, the excited states of G-quartet and its complexes with lithium, sodium and potassium were studied by employing time-dependent density functional theory. The findings indicate that vertical excitations from the optimized ground state involve transitions from several bases, whereas excitations from the optimized lowest excited state include transitions from one base. The charge-transfer character of these states was analyzed. It was shown that the cations are able to modify positions of the maxima of the fluorescence spectra of the complexes.

Neisseria gonorrhoeae MutS Affects Pilin Antigenic Variation through Mismatch Correction and Not bypilEGuanine Quartet Binding

ABSTRACTMany pathogens use homologous recombination to vary surface antigens to avoid immune surveillance.Neisseria gonorrhoeaeachieves this in part by changing the properties of its surface pili in a process called pilin antigenic variation (AV). Pilin AV occurs by high-frequency gene conversion reactions that transfer silentpilSsequences into the expressedpilElocus and requires the formation of an upstream guanine quartet (G4) DNA structure to initiate this process. The MutS and MutL proteins of the mismatch correction (MMC) system act to correct mismatches after replication and prevent homeologous (i.e., partially homologous) recombination, but MutS orthologs can also bind to G4 structures. A previous study showed that mutation of MutS resulted in a 3-fold increase in pilin AV, which could be due to the loss of MutS antirecombination properties or loss of G4 binding. We tested two site-directed separation-of-function MutS mutants that are both predicted to bind to G4s but are not able to perform MMC. Pilus phase variation assays and DNA sequence analysis ofpilEvariants produced in these mutants showed that all threemutSmutants and amutLmutant had similar increased frequencies of pilin AV. Moreover, themutSmutants all showed similar increased levels of pilin AV-dependent synthetic lethality. These results show that antirecombination by MMC is the reason for the effect that MutS has on pilin AV and is not due topilEG4 binding by MutS.IMPORTANCENeisseria gonorrhoeaecontinually changes its outer surface proteins to avoid recognition by the immune system.N. gonorrhoeaealters the antigenicity of the pilus by directed recombination between partially homologous pilin copies in a process that requires a guanine quartet (G4) structure. The MutS protein of the mismatch correction (MMC) system prevents recombination between partially homologous sequences and can also bind to G4s. We confirmed that loss of MMC increases the frequency of pilin antigenic variation and that two MutS mutants that are predicted to separate the two different functions of MutS inhibit pilin variation similarly to a complete-loss-of-function mutant, suggesting that interaction of MutS with the G4 structure is not a major factor in this process.

Cobalt(iii)porphyrin to target G-quadruplex DNA

A bulky cationic cobalt(iii) porphyrin carrying two water molecules as axial ligands interacts in a π-stacking like mode with the 5′-external guanine quartet of G-quadruplex DNA.