DNA Interstrand Cross‐Link Formation Using Furan as a Masked Reactive Aldehyde

Carrette, Lieselot L. G.; Gyssels, Ellen; Madder, Annemieke

doi:10.1002/0471142700.nc0512s54

Cited by 8 publications

(13 citation statements)

References 16 publications

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“…It should be noted that the relative reactivity of the nucleobase reflects their true reactivities as they were compared under the same conditions without complication from the base‐pairing/stacking ability of different nucleobases. Nevertheless, the reactivity pattern of C and A towards crosslinking with furan is in line with other studies [1a,21,23a,24,25,29,34] . Remarkably, the G base was for the first time found to participate in the crosslinking reaction with furan.…”

Section: Discussionsupporting

confidence: 91%

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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Section: Discussionsupporting

confidence: 91%

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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“…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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“…1). [18][19][20][21][22] We have shown that furan moieties can be easily incorporated in oligodeoxynucleotides (ODNs) in view of the stability and wide commercial availability of furan derivatives. Furan modified ODNs can be activated by oxidation to a very reactive oxo-butenal that quickly reacts with the exocyclic amine of the opposite base resulting in selective and high yielding interstrand cross-link (ICL) formation.…”

Section: Introductionmentioning

confidence: 99%

A mildly inducible and selective cross-link methodology for RNA duplexes

et al. 2014

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We here report on the furan oxidation methodology for interstrand cross-linking of RNA duplexes, which have a different structure and are more stiff, reactive and labile than their DNA counterparts. Through this mildly inducible approach, natural unmodified RNA can be selectively cross-linked in high yield. The method therefore has direct applications in the increasing number of RNA based technologies.

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DNA Interstrand Cross‐Link Formation Using Furan as a Masked Reactive Aldehyde

Cited by 8 publications

References 16 publications

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

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

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

A mildly inducible and selective cross-link methodology for RNA duplexes

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