# Distinctive Nucleic Acid Recognition by Lysine-Embedded Phenanthridine Peptides

## TL;DR

Researchers developed new peptides that can detect DNA and RNA with high specificity, using lysine to enhance binding and distinguish between different nucleic acid sequences.

## Contribution

The study introduces lysine-embedded phenanthridine peptides that show improved nucleic acid recognition and selective fluorimetric responses.

## Key findings

- Lysine-substituted peptides showed stronger DNA and RNA binding than glycine-containing compounds.
- Compound 23 selectively responded to AT and ATT polynucleotides and induced triplex formation.
- Compound 23 recognized GC-rich DNA through distinct CD signals and had a binding constant of 2.5 × 10⁷ M⁻¹.

## Abstract

Three new phenanthridine peptide derivatives (19, 22, and 23) were synthesized to explore their potential as spectrophotometric probes for DNA and RNA. UV/Vis and circular dichroism (CD) spectra, mass spectroscopy, and computational analysis confirmed the presence of intramolecular interactions in all three compounds. Computational analysis revealed that compounds alternate between bent and open conformations, highlighting the latter’s crucial influence on successful polynucleotide recognition. Substituting one glycine with lysine in two regioisomers (22, 23) resulted in stronger binding interactions with DNA and RNA than for a compound containing two glycines (19), thus emphasizing the importance of lysine. The regioisomer with lysine closer to the phenanthridine ring (23) exhibited a dual and selective fluorimetric response with non-alternating AT and ATT polynucleotides and induction of triplex formation from the AT duplex. The best binding constant (K) with a value of 2.5 × 107 M−1 was obtained for the interaction with AT and ATT polynucleotides. Furthermore, apart from distinguishing between different types of ds-DNA and ds-RNA, the same compound could recognize GC-rich DNA through distinct induced CD signals.