Conjugation of N -(3-(9-Ethynyl-6H -indolo[2,3-b ]quinoxalin-6-yl)propyl)-2,2,2-trifluoroacetamide Intercalator to a Triplex Forming Oligonucleotide, a Three-Way Junction, and a G-Quadruplex

2019 ◽  
Vol 2019 (27) ◽  
pp. 4362-4371
Author(s):  
Amany M. A. Osman ◽  
Erik B. Pedersen
Keyword(s):  
G Quadruplex ◽  
Triplex Forming Oligonucleotide

scholarly journals Oligonucleotide Binding to Non-B-DNA in MYC

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 1000
Author(s):  
Tea Umek ◽  
Karin Sollander ◽  
Helen Bergquist ◽  
Jesper Wengel ◽  
Karin E. Lundin ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Immunoglobulin Gene ◽  
Mobility Shift ◽  
Cleavage Assay ◽  
G Quadruplex ◽  
Myc Gene ◽  
Strand Invasion ◽  
Mobility Shift Assay ◽  
Triplex Forming Oligonucleotide

MYC, originally named c-myc, is an oncogene deregulated in many different forms of cancer. Translocation of the MYC gene to an immunoglobulin gene leads to an overexpression and the development of Burkitt’s lymphoma (BL) [1]. Sporadic BL constitutes one subgroup where one of the translocation sites is located at the 5′-vicinity of the two major MYC promoters P1 and P2. A non-B-DNA forming sequence within this region has been reported with the ability to form an intramolecular triplex (H-DNA) or a G-quadruplex[2,3]. We have examined triplex formation at this site first by using a 17 bp triplex-forming oligonucleotide (TFO) and a double strand DNA (dsDNA) target corresponding to the MYC sequence. An antiparallel purine-motif triplex was detected using electrophoretic mobility shift assay. Furthermore, we probed for H-DNA formation using the BQQ-OP based triplex-specific cleavage assay, which indicated the formation of the structure in the supercoiled plasmid containing the corresponding region of the MYC promoter. Targeting non-B-DNA structures has therapeutic potential; therefore, we investigated their influence on strand-invasion of anti-gene oligonucleotides (ON)s. We show that in vitro, non-B-DNA formation at the vicinity of the ON target site facilitates dsDNA strand-invasion of the anti-gene ONs.

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