Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA2DNA triplexes

Pyrene derivatives can be incorporated into nucleic acid analogs in order to obtain switchable probes or supramolecular architectures. In this paper, peptide nucleic acids (PNAs) containing 1 to 3 1-pyreneacetic acid units (PNA1–6) with a sequence with prevalence of pyrimidine bases, complementary to cystic fibrosis W1282X point mutation were synthesized. These compounds showed sequence-selective switch-on of pyrene excimer emission in the presence of target DNA, due to PNA2DNA triplex formation, with stability depending on the number and positioning of the pyrene units along the chain. An increase in triplex stability and a very high mismatch-selectivity, derived from combined stacking and base-pairing interactions, were found for PNA2, bearing two distant pyrene units.

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Porous supramolecular architectures based on π-stacking interactions between discrete metal–adenine entities and theobromine/caffeine methylxanthines

Acta Crystallographica Section A Foundations and Advances ◽

10.1107/s2053273318089945 ◽

2018 ◽

Vol 74 (a2) ◽

pp. e350-e351

Author(s):

Jon Pascual Colino ◽

Maite Perfecto-Irigaray ◽

Garikoitz Beobide Pacheco ◽

Oscar Castillo Garcia ◽

Antonio Luque Arrebola ◽

...

Keyword(s):

Stacking Interactions ◽

Supramolecular Architectures ◽

Π Stacking

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Unlocked nucleic acids: implications of increased conformational flexibility for RNA/DNA triplex formation

Biochemical Journal ◽

10.1042/bj20141023 ◽

2014 ◽

Vol 464 (2) ◽

pp. 203-211 ◽

Cited By ~ 13

Author(s):

Weronika Kotkowiak ◽

Michał Kotkowiak ◽

Ryszard Kierzek ◽

Anna Pasternak

Keyword(s):

Nucleic Acids ◽

Conformational Flexibility ◽

Hairpin Structure ◽

Triplex Formation ◽

Dna Triplex

UNA moieties within the TFO strongly destabilize triplexes. Introduction of UNA into specific positions in the hairpin structure is energetically favourable for triplex formation. UNA increases the resistance of the oligonucleotides to serum nucleases when incorporated at specific hairpin positions.

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Analyzing RNA–DNA Triplex Formation in Chromatin

Methods in Molecular Biology - RNA-Chromatin Interactions ◽

10.1007/978-1-0716-0680-3_17 ◽

2020 ◽

pp. 247-254

Author(s):

Rodrigo Maldonado ◽

Gernot Längst

Keyword(s):

Triplex Formation ◽

Dna Triplex

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A High-Throughput Assay for DNA Topoisomerases and Other Enzymes, Based on DNA Triplex Formation

Methods in Molecular Biology - Drug-DNA Interaction Protocols ◽

10.1007/978-1-60327-418-0_16 ◽

2009 ◽

pp. 257-266 ◽

Cited By ~ 5

Author(s):

Matthew R. Burrell ◽

Nicolas P. Burton ◽

Anthony Maxwell

Keyword(s):

High Throughput ◽

Dna Topoisomerases ◽

Triplex Formation ◽

Dna Triplex ◽

High Throughput Assay

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Inhibition of Interleukin-4- and CD40-induced IgE Germline Gene Promoter Activity by 2′-Aminoethoxy-modified Triplex-forming Oligonucleotides

Journal of Biological Chemistry ◽

10.1074/jbc.m010260200 ◽

2001 ◽

Vol 276 (15) ◽

pp. 11759-11765 ◽

Cited By ~ 16

Author(s):

Adrian M. Stütz ◽

Jutta Hoeck ◽

Francois Natt ◽

Bernard Cuenoud ◽

Maximilian Woisetschläger

Keyword(s):

B Cells ◽

Critical Role ◽

Gene Promoter ◽

Gene Induction ◽

Modified Oligonucleotides ◽

Germline Gene ◽

Triplex Formation ◽

Human B Cells ◽

Dna Triplex

Elevated levels of IgE are intimately associated with a number of allergic diseases, such as allergic rhinitis or asthma. Therefore, prevention of IgE production in human B-cells represents an attractive therapeutic target. IL-4-induced IgE germline gene transcription represents a crucial early step during IgE isotype switch differentiation. Gene induction is orchestrated by the coordinated action of the transcription factors STAT6 (signal transducer and activator of transcription), NF-κB, PU.1, and C/EBP. This study shows that 2′-aminoethoxy-modified oligonucleotides, which partially overlap with the STAT6 and the adjacent PU.1/NF-κB binding site, inhibit DNA binding of all three proteins with high affinity in a dose- and time-dependent fashionin vitro. Loss of protein binding correlated strongly with increasing DNA triplex formation. Importantly, the oligomers also effectively displaced pre-bound recombinant NF-κB p50 from double-stranded DNAin vitro. Functionally, the oligonucleotides led to a selective inhibition of IL-4-induced reporter gene activity from a construct driven by the IgE germline gene promoter in human B-cells. These data confirm the critical role of this cytokine-responsive regulatory region in IgE germline gene induction and further support the concept of specific modulation of gene expression by DNA triplex formation induced with chemically modified oligonucleotides.

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