Telomeric regions containing G-quadruplex (G4) structures play a pivotal role in the development of cancers. The development of specific binders for G4s is thus of great interest in order to gain a deeper understanding of the role of these structures, and to ultimately develop new anticancer drug candidates. For several years, Ru complexes have been studied as efficient probes for DNA. Interest in these complexes stems mainly from the tunability of their structures and properties, and the possibility of using light excitation as a tool to probe their environment or to selectively trigger their reaction with a biological target. Herein, we report on the synthesis and thorough study of new Ru complexes based on a novel dipyrazino[2,3-a:2',3'-h]phenazine ligand (dph), obtained through a Chichibabin-like reaction. Luminescence experiments, surface plasmon resonance (SPR), and computational studies have demonstrated that these complexes behave as selective probes for G-quadruplex structures.
Rapid
antigen tests are currently used for population screening
of COVID-19. However, they lack sensitivity and utilize antibodies
as receptors, which can only function in narrow temperature and pH
ranges. Consequently, molecularly imprinted polymer nanoparticles
(nanoMIPs) are synthetized with a fast (2 h) and scalable process
using merely a tiny SARS-CoV-2 fragment (∼10 amino acids).
The nanoMIPs rival the affinity of SARS-CoV-2 antibodies under standard
testing conditions and surpass them at elevated temperatures or in
acidic media. Therefore, nanoMIP sensors possess clear advantages
over antibody-based assays as they can function in various challenging
media. A thermal assay is developed with nanoMIPs electrografted onto
screen-printed electrodes to accurately quantify SARS-CoV-2 antigens.
Heat transfer-based measurements demonstrate superior detection limits
compared to commercial rapid antigen tests and most antigen tests
from the literature for both the alpha (∼9.9 fg mL
–1
) and delta (∼6.1 fg mL
–1
) variants of the
spike protein. A prototype assay is developed, which can rapidly (∼15
min) validate clinical patient samples with excellent sensitivity
and specificity. The straightforward epitope imprinting method and
high robustness of nanoMIPs produce a SARS-CoV-2 sensor with significant
commercial potential for population screening, in addition to the
possibility of measurements in diagnostically challenging environments.
G-rich DNA oligonucleotides derived from the promoter region of the HIV-1 long terminal repeat (LTR) were assembled onto an addressable cyclopeptide platform through sequential oxime ligation, a thiol-iodoacetamide SN2 reaction, and copper-catalyzed azide-alkyne cycloaddition reactions. The resulting conjugate was shown to fold into a highly stable antiparallel G4 architecture as demonstrated by UV, circular dichroism (CD), and NMR spectroscopic analysis. The binding affinities of six state-of-the-art G4-binding ligands toward the HIV-G4 structure were compared to those obtained with a telomeric G4 structure and a hairpin structure. Surface plasmon resonance binding analysis provides new insights into the binding mode of broadly exploited G4 chemical probes and further suggests that potent and selective recognition of viral G4 structures of functional significance might be achieved.
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