The Neuroblastoma RAS (NRAS) oncogene homologue plays crucial roles in diverse cellular processes such as cell proliferation, survival, and differentiation. Several strategies have been developed to inhibit NRAS or its downstream effectors; however, there is no effective drug available to treat NRAS-driven cancers and thus new approaches are needed to be established. The mRNA sequence expressing NRAS containing several guanine(G)-rich regions may form quadruplex structures (G4s) and regulate NRAS translation.
View Article and Find Full Text PDFMitochondria are important drug targets for anticancer and other disease therapies. Certain human mitochondrial DNA sequences capable of forming G-quadruplex structures (G4s) are emerging drug targets of small molecules. Despite some mitochondria-selective ligands being reported for drug delivery against cancers, the ligand design is mostly limited to the triphenylphosphonium scaffold.
View Article and Find Full Text PDFTwenty-seven rosmarinic acid derivatives were synthesized, among which compound RA-N8 exhibited the most potent antibacterial ability. The minimum inhibition concentration of RA-N8 against both S. aureus (ATCC 29213) and MRSA (ATCC BAA41 and ATCC 43300) was found to be 6 μg/mL, and RA-N8 killed E.
View Article and Find Full Text PDFThe development of site-specific, target-selective and biocompatible small molecule ligands as a fluorescent tool for real-time study of cellular functions of RNA G-quadruplexes (G4s), which are associated with human cancers, is of significance in cancer biology. We report a fluorescent ligand that is a cytoplasm-specific and RNA G4-selective fluorescent biosensor in live HeLa cells. The in vitro results show that the ligand is highly selective targeting RNA G4s including VEGF, NRAS, BCL2 and TERRA.
View Article and Find Full Text PDFThe formation of G-quadruplex structures (G4s) from guanine (G)-rich nucleic acid sequences of DNA and RNA stabilized with monovalent cations, typically K and Na, under physiological conditions, has been verified experimentally and some of them have high-resolution NMR or -ray crystal structures; however, the biofunction of these special noncanonical secondary structures of nucleic acids has not been fully understood and their existence is still controversial at present. It is generally believed that the folding and unfolding of G4s is a transient process. Accumulating evidence has shown that G4s may play a role in the regulation of certain important cellular functions including telomere maintenance, replication, transcription and translation.
View Article and Find Full Text PDFBiochim Biophys Acta Proteins Proteom
October 2022
Bacteria expressing NDM-1 have been labeled as superbugs because it confers upon them resistance to a broad range of β-lactam antibiotics. The enzyme has a di‑zinc active centre, with the Zn2 site extensively studied. The roles of active-site Zn1 ligand residues are, however, still not fully understood.
View Article and Find Full Text PDFA series of isatin derivatives bearing three different substituent groups at the N-1, C-3 and C-5 positions of the isatin scaffold were systematically designed and synthesized to study the structure-activity relationship of their inhibition of bacterial peptidoglycan glycosyltransferase (PGT) activity and antimicrobial susceptibility against , and methicillin-resistant (MRSA (BAA41)) strains. The substituents at these sites are pointing towards three different directions from the isatin scaffold to interact with the amino acid residues in the binding pocket of PGT. Comparative studies of their structure-activity relationship allow us to gain better understanding of the direction of the substituents that contribute critical interactions leading to inhibition activity against the bacterial enzyme.
View Article and Find Full Text PDFSelective modification of the N-terminus of peptides and proteins is a promising strategy for single site modification methods. Here we report N-terminal selective modification of peptides and proteins by using 2-ethynylbenzaldehydes (2-EBA) for the production of well-defined bioconjugates. After reaction screening with a series of 2-EBA, excellent N-terminal selectivity is achieved by the reaction in slightly acidic phosphate-buffered saline using 2-EBA with electron-donating substituents.
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