Predictive Model for the Sequence-Dependent Fluorogenic Response of Forced-Intercalation Peptide Nucleic Acid

Itamar Peled, Eylon Yavin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


The forced-intercalation peptide nucleic acid (FIT-PNA) concept, introduced by Seitz and co-workers, is based on replacing a nucleobase of the PNA sequence with a cyanine dye (such as thiazole orange). The cyanine dye is thus a surrogate base that is forced to intercalate in the duplex (e.g., PNA:DNA). This allows single-mismatch sensitivity as the introduction of a mismatch in the vicinity of the dye increases freedom of motion and leads to a significant depletion of its fluorescence because of the free rotation of the monomethine bond separating the two π-systems of the cyanine dye. Herein, we designed and synthesized six FIT-PNA probes, featuring bisquinoline (BisQ), a red-emitting cyanine dye recently developed in our laboratory for FIT-PNAs. By following PNA-DNA duplex fluorescence, we found new sequence-based factors governing the fluorescence response to the mismatched FIT-PNA:DNA duplex. Fluorogenic properties are correlated with the π-stacking energy of three distinctive base pair steps (BPSs) in the PNA:DNA duplex. The first two are the two BPSs opposite BisQ, whereas the third is the BPS of the mismatch position, which presumably becomes unstacked due to the mismatch. We suggest a predictive model for FIT-PNA single-mismatch detection mechanism, a model that can be used in future research to improve FIT-PNA design.

Original languageAmerican English
Pages (from-to)3813-3818
Number of pages6
JournalACS Omega
Issue number4
StatePublished - 30 Apr 2018

Bibliographical note

Funding Information:
This research was supported by the Israel Science Foundation (grant no. 476/17). E.Y. acknowledges the David R. Bloom Center for Pharmacy for financial support.

Publisher Copyright:
© 2018 American Chemical Society.


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