UltraFast PhotoInduced double duplex DNA invasion into a 400-mer dsDNA target.
3-cyanovinylcarbazole
Artificial restriction enzyme
Double-duplex invasion
Photo-cross-linking
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
26 Dec 2023
26 Dec 2023
Historique:
received:
10
09
2023
revised:
13
12
2023
accepted:
23
12
2023
medline:
29
12
2023
pubmed:
29
12
2023
entrez:
28
12
2023
Statut:
aheadofprint
Résumé
Natural DNA restriction enzymes bind duplex DNA with high affinity at multiple sites; however, for some of the artificial chemical-based restriction moieties, invasion of the double-strand for efficient cleavage is an obstacle. We have previously reported photo-induced double-duplex invasion (pDDI) using 3-cyanovinylcarbazole (K)-containing probes for both the target strands that photo-crosslink with pyrimidine bases in a sequence-specific manner on both the strands, stabilizing the opened double-strand for cleavage. The drawback of the pDDI was low efficiency due to inter-probe cross-linking, solved by the inclusion of 5-cyano-uridine at -1 position on the complimentary strand with respect to K in both probes. Although this led to reduced inter-probe cross-linking, the pDDI efficiency was still low. Here, we report that inter-probe cross-linking and intra-probe cross-linking of a single probe is also leading to reduced pDDI efficiency. We addressed this problem by designing DDI probes to inhibit both inter-probe and intra-probe cross-linking. Based on the new design of pDDI probe with 5-cyano uridine led to a drastic increase in the efficiency of pDDI in (400-mer) double-stranded DNA with only 1 s of photo-irradiation.
Sections du résumé
BACKGROUND
BACKGROUND
Natural DNA restriction enzymes bind duplex DNA with high affinity at multiple sites; however, for some of the artificial chemical-based restriction moieties, invasion of the double-strand for efficient cleavage is an obstacle. We have previously reported photo-induced double-duplex invasion (pDDI) using 3-cyanovinylcarbazole (K)-containing probes for both the target strands that photo-crosslink with pyrimidine bases in a sequence-specific manner on both the strands, stabilizing the opened double-strand for cleavage. The drawback of the pDDI was low efficiency due to inter-probe cross-linking, solved by the inclusion of 5-cyano-uridine at -1 position on the complimentary strand with respect to K in both probes. Although this led to reduced inter-probe cross-linking, the pDDI efficiency was still low.
RESULTS
RESULTS
Here, we report that inter-probe cross-linking and intra-probe cross-linking of a single probe is also leading to reduced pDDI efficiency. We addressed this problem by designing DDI probes to inhibit both inter-probe and intra-probe cross-linking.
CONCLUSION
CONCLUSIONS
Based on the new design of pDDI probe with 5-cyano uridine led to a drastic increase in the efficiency of pDDI in (400-mer) double-stranded DNA with only 1 s of photo-irradiation.
Identifiants
pubmed: 38154604
pii: S0960-894X(23)00475-4
doi: 10.1016/j.bmcl.2023.129597
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
129597Informations de copyright
Copyright © 2023. Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.