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- W4387395560 abstract "Abstract Noncanonical secondary structures formed by Guanine-rich DNA sequences fold into four-stranded structures called the G-quadruplexes (G4s). Targeting G-quadruplexes is considered an attractive approach toward drug intervention. Recently, we have identified and published G4 forming motifs in regulatory regions of different cancer stem cell markers (CD13, CD19, CD24 and CD38). Hence, in this study, a set of biophysical and biochemical techniques like Circular Dichroism (CD), UV-Thermal denaturation (UV- T m ) and polyacrylamide gel electrophoresis (PAGE) were used to study the targeting of G4s of stem cell markers with designed short peptide (named as QW10). Our CD studies showed that G4 sequences of stem cell markers formed mixed G-quadruplexes in 100 mM Na + , 100mM K + and 100 mM K + + 40wt% PEG 200. On titrating these structures with an increasing concentration of QW10 peptide, we observed a significant decrease in CD intensity followed by the complete disappearance of G4 CD signatures confirming their destabilization not only in dilute conditions but also under cell-mimicking molecular crowding conditions. Our results for the UV-thermal melting showed a significant decrease in the T m values which confirmed the significant destabilization of G4 structures into dimeric structures stabilized by stacking energies probably due to the intercalation of tryptophan present in QW10 peptide. Our electrophoretic mobility shift assay confirmed the destabilization of G4 structures. Fluorescence results showed the formation of high-affinity G4 complex-peptide complex with binding affinities in the micromolar ( µ M) range of 2 µ M to 8 µ M in different ionic conditions. First time, this study may give insight into the use of peptides as leads for the development of more potent and selective ligands to regulate the potential therapeutic applications of cancer stem cell markers." @default.
- W4387395560 created "2023-10-07" @default.
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- W4387395560 date "2023-10-06" @default.
- W4387395560 modified "2023-10-07" @default.
- W4387395560 title "Targeting G4 motifs of various stem cell makers with designed peptide for therapeutic applications" @default.
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- W4387395560 doi "https://doi.org/10.21203/rs.3.rs-3382048/v1" @default.
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