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Series GSE148419 Query DataSets for GSE148419
Status Public on Jul 28, 2020
Title Custom DNA microarrays reveal the selective recognition of BMVC to MYC promoter G-quadruplex: a large-scale assessment of ligand binding selectivity
Organism synthetic construct
Experiment type Other
Summary G-quadruplexes (G4) are considered new drug targets for human diseases such as cancer. More than 10,000 G4s have been discovered in human chromatin, posing challenges for assessing the selectivity of a G4-interactive ligand. 3,6-bis(1-Methyl-4-vinylpyridinium) carbazole diiodide (BMVC) is the first fluorescent small molecule for G4 detection in vivo. Our previous structural study shows that BMVC binds to the MYC promoter G4 (MycG4) with high specificity. Here, we utilize high-throughput, large-scale custom DNA G4 microarrays to analyze the G4-binding selectivity of BMVC. BMVC preferentially binds to the parallel MycG4 and selectively recognizes flanking sequences of parallel G4s, especially the 3′-flanking thymine. Importantly, the microarray results are confirmed by orthogonal NMR and fluorescence binding analyses. Our study demonstrates the potential of custom G4 microarrays as a platform to broadly and unbiasedly assess the binding selectivity of G4-interactive ligands, and to help understand the properties that govern molecular recognition.
Overall design Binding microarray experiments were performed for G-quadruplex (G4) DNA interacting small molecules pyridostatin (PDS), BMVC. Briefly, the binding experiments involved incubating Cy5-conjugated PDS with unlabeled molecules (PDS and BMVC) to 180K feature Agilent microarrays pre-incubated with 100mM potassium chloride (KCl) in order to determine the binding preferences of the unlabelled molecules to G4-forming sequences.
Contributor(s) Tillo D
Citation(s) 32751510
Submission date Apr 09, 2020
Last update date Aug 31, 2020
Contact name Desiree Tillo
Phone +1-240-760-7289
Organization name NIH/NCI
Street address 41 Center Dr, Room D310
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL28372 Agilent-086005 ASSAD_G4_D4 G4125A array
Samples (12)
GSM4469939 G4_d4_Cy5-PDS_1uM_plus_0uM_BMVC_ctrl_rep1
GSM4469940 G4_d4_Cy5-PDS_1uM_plus_0uM_BMVC_ctrl_rep2
GSM4469941 G4_d4_Cy5-PDS_1uM_plus_3uM_PDS_comp_rep1
BioProject PRJNA624167

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE148419_RAW.tar 41.9 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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