Distinctive Nucleic Acid Recognition by Lysine-Embedded Phenanthridine Peptides.

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.

The guanidiniocarbonylpyrrole-fluorophore conjugates as theragnostic tools for dipeptidyl peptidase III monitoring and inhibition.

Study of seven new guanidiniocarbonylpyrrole (GCP)-fluorophore conjugates interactions with dipeptidyl peptidase III (DPP III) showed that all compounds bind strongly (Ks ≈ µM) to enzyme active site, but with very different fluorimetric response (varying from quenching to strong increase), dependent on the fluorophore type and intramolecular pre-organisation of molecule. Positively charged lysine side chain improved significantly compound solubility but diminished fluorescence increase upon DPP III binding and completely abolished inhibitory effect on DPP III activity, whereas linker-neutral analogues showed stronger emission increase and were efficient enzyme inhibitors. By far the best fluorimetric response and inhibitive properties showed cyanine-GCP analogue, thus being promising lead compound for both enzyme sensing and bio-activity inhibiting (theragnostic) studies of DPP III in the future.Communicated by Ramaswamy H. Sarma.

DNA/RNA recognition controlled by the glycine linker and the guanidine moiety of phenanthridine peptides.

The binding of four phenanthridine-guanidine peptides to DNA/RNA was evaluated via spectrophotometric/microcalorimetric methods and computations. The minor structural modifications-the type of the guanidine group (pyrrole guanidine (GCP) and arginine) and the linker length (presence or absence of glycine)-greatly affected the conformation of compounds and consequently the binding to double- (ds-) and single-stranded (ss-) polynucleotides. GCP peptide with shorter linker was able to distinguish between RNA (A-helix) and DNA (B-helix) by different circular dichroism response at 295 nm and thus can be used as a chiral probe. Opposed to the dominant stretched conformation of GCP peptide with shorter linker, the more flexible and longer linker of its analogue enabled the molecule to adopt the intramolecularly stacked form which resulted in weaker yet selective binding to DNA. Beside efficient organization of ss-polynucleotide structures, GCP peptide with shorter linker bound stronger to ss-DNA/RNA compared to arginine peptides which emphasize the importance of GCP unit.

A short, rigid linker between pyrene and guanidiniocarbonyl-pyrrole induced a new set of spectroscopic responses to the ds-DNA secondary structure.

A novel pyrene-guanidiniocarbonyl-pyrrole dye, characterised by a short, rigid linker between the two chromophores, interacts strongly with ds-DNA but only negligibly with ds-RNA. Under neutral conditions the dye shows strong selectivity toward AT-DNA (with respect to GC-DNA). Binding is accompanied by a specific ICD band at 350 nm and fluorescence quenching for all DNAs/RNAs studied. At pH 5 the affinity of the dye is reversed, now favouring GC-DNA over AT-DNA. A strong emission increase for AT-DNA is observed but with quenching for GC-DNA.