Triplex Crosslinking through Furan Oxidation Requires Perturbation of the Structured Triple‐Helix

Gyssels, Ellen; Carrette, Lieselot L. G.; Vercruysse, Emma; Stevens, Kristof; Madder, Annemieke

doi:10.1002/cbic.201402602

Cited by 7 publications

(12 citation statements)

References 53 publications

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“…In contrast to the earlier developed DNA based probes, 33 we expected the here developed PNA-furan probes to offer the possibility to target double stranded DNA. We thus tested their ability to form ICLs in a strand displacement test.…”

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confidence: 89%

Furan-PNA: a mildly inducible irreversible interstrand crosslinking system targeting single and double stranded DNA

et al. 2016

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confidence: 89%

Furan-PNA: a mildly inducible irreversible interstrand crosslinking system targeting single and double stranded DNA

et al. 2016

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“…Our group therefore started exploring the use of furan moieties as masked aldehydes for a novel cross-linking technology. [55][56][57][58][59][60][61][62][63][64][65][66][67] Owing to the stability of the furan moiety before oxidation, a large series of furan derivatives is readily available. Moreover, the moiety is compatible with most of the standard chemistries used for modified nucleoside, amino acid, ODN and peptide synthesis.…”

Section: A Maddermentioning

confidence: 99%

Furan oxidation based cross-linking: a new approach for the study and targeting of nucleic acid and protein interactions

et al. 2016

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Furan mediated nucleic acid cross-linking, initially developed for DNA interstrand duplex cross-linking, has matured into a versatile tool for the study of protein and nucleic acid interactions, ready to face its applications. The methodology was initially developed for easy and clean chemical generation of DNA interstrand cross-linked duplexes, but has been further expanded for use with other probes, targets and triggers, now allowing mild biologically significant cross-linking with potential therapeutic benefit. It was shown that the methodology could be repurposed for RNA interstrand cross-linking, which is very relevant in today's antisense approaches or miRNA target identification endeavors. This further illustrates the furan oxidation method's generality and mildness, especially when using red light for oxidation. A complementary antigene approach has been explored through duplex targeting with furan modified triplex forming oligonucleotides (TFOs) and DNA binding proteins. Also targeting of peptides and proteins by furan-modified DNA and peptides has been explored. Thorough methodology examination exploring variable reaction conditions in combination with a series of different furan-modified building blocks and application of different activation signals resulted in a detailed understanding of the mechanisms involved and factors influencing the yield and selectivity of the reaction. In order to draw the bigger picture of the scope and limitations of furan-oxidation cross-linking, we here provide a unique side by side comparison and discussion of our published data, supplemented with unpublished results, providing a clear performance report of the currently established furan toolbox and its application potential in various biomacromolecular complexes.

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“…The results are also in line with another related work that studied the crosslinking reaction of furan-modified DNAs at the internal position and the 3'-end of the DNA strand with a duplex DNA via the triplex formation. [22] In this case, the furan was incorporated as a base surrogate, and it was observed that the crosslinking with the internally furan-modified probe could take place only with the single-stranded DNA target but not with the duplex DNA target due to the unavailability of the nucleobase. On the other hand, the crosslink readily formed in the case of 3'-furan modified probe with both single-stranded and duplex DNA targets.…”

Section: Discussionmentioning

confidence: 99%

“…[21] Furthermore, crosslinkable ODN probes were applied to target double-stranded DNA by triplex formation. [22] A similar strategy has been applied to target proteins by crosslinking with a furan-modified peptide ligand. [23] Interestingly, the crosslinking spontaneously occurred in several cell lines, presumably via the oxidation by endogenously produced reactive oxygen species.…”

Section: Introductionmentioning

confidence: 99%

“…Similar crosslinking reactions were also applicable to RNA targets, and a specific crosslinking product was observed with a complementary C base in a 42 % yield [21] . Furthermore, crosslinkable ODN probes were applied to target double‐stranded DNA by triplex formation [22] . A similar strategy has been applied to target proteins by crosslinking with a furan‐modified peptide ligand [23] .…”

Section: Introductionmentioning

confidence: 99%

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Pyrrolidinyl Peptide Nucleic Acid Probes Capable of Crosslinking with DNA: Effects of Terminal and Internal Modifications on Crosslink Efficiency

Muangkaew

Vilaivan

2020

ChemBioChem

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In this study, we describe a furan-modified acpcPNA as a probe that can form an interstrand crosslink (ICL) with its DNA target upon activation with N-bromosuccinimide (NBS). To overcome the problem of furan instability under acidic conditions, a simple and versatile post-synthetic methodology for the attachment of the furan group to the PNA probe was developed. Unlike in other designs, the furan was placed at the end of the PNA molecule or tethered to the PNA backbone with all the base pairs in the PNA • DNA duplexes fully preserved. Hence, the true reactivity of each nucleobase towards the crosslinking could be compared. We show that all DNA bases except T could participate in the crosslinking reaction when the furan was placed at the end of the PNA strand. The crosslinking process was sensitive to mispairing, and lower crosslinking efficiency was observed in the presence of a base-mismatch in the PNA • DNA duplex. In contrast, when the furan was placed at internal positions of the acpcPNA • DNA duplex, no ICL was observed; this was explained by the inability of a hydrogenbonded nucleobase to participate in the crosslinking reaction. The crosslinking efficiency was considerably improved, despite lower duplex stability, when an unpaired base (in the form of Cinsertion) was present in the complementary DNA strand close to the furan modification site.

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Triplex Crosslinking through Furan Oxidation Requires Perturbation of the Structured Triple‐Helix

Cited by 7 publications

References 53 publications

Furan-PNA: a mildly inducible irreversible interstrand crosslinking system targeting single and double stranded DNA

Furan-PNA: a mildly inducible irreversible interstrand crosslinking system targeting single and double stranded DNA

Furan oxidation based cross-linking: a new approach for the study and targeting of nucleic acid and protein interactions

Pyrrolidinyl Peptide Nucleic Acid Probes Capable of Crosslinking with DNA: Effects of Terminal and Internal Modifications on Crosslink Efficiency

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