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The intermolecular interactions of a homoaromatic tripeptide, H-Tyr-Tyr-Tyr-OH (YYY) with model double-stranded (ds) DNA (ct-DNA) have been investigated by isothermal titration calorimetric (ITC) method along with various biophysical techniques such as fluorescence, time correlated single photon counting (TCSPC) and circular dichroism (CD) spectroscopy. The binding affinity [log (K) at 25 °C] of the YYY to ct-DNA is calculated as ≈4.3. The binding mode of the YYY to ds-DNA is elucidated by fluorescence intercalator displacement (FID) assay, melting temperature analysis, viscosity measurement and salt-induced fluorescence quenching study. The studies establish that the YYY recognizes the groove of the ct-DNA. The temperature dependent ITC studies show that the binding interaction is thermodynamically favourable. The compensation between enthalpy and entropy leads to the overall Gibbs free energy change almost invariant. Finally, the generality of the YYY to recognize ds-DNA has been analyzed with other model ds-DNA, ds26, which reveals almost similar binding affinity of the YYY as ct-DNA. The studies elucidate both the spectroscopic and calorimetric insight of the interactions of a homoaromatic tripeptide with ds-DNA and hold the promise of future applications as DNA targeting drug., (Copyright © 2018. Published by Elsevier B.V.)

G‐quadruplex (G4) is one of the non‐canonical nucleic acid structures that regulate multiple key biological processes. The formation of G4 hinders the progression of cancer. The molecular entities which can stabilize the G4 structure are very important to design anticancer therapeutics. Herein, it is described that a synthetic dendron‐like peptide, Cδ3‐(YYEE)‐E co‐assembles with G4 DNA in aqueous buffer containing Na+ ions. Various orthogonal biophysical studies have established the co‐assembly phenomenon. In silico, molecular docking studies also corroborate the results obtained from biophysical experiments. Importantly, the co‐assembly enhances the thermal stability of G4 DNA compared to free G4 DNA. The peptide inhibits the activity of telomerase enzyme which is found to be over‐expressed in most of the cancer cells and also down‐regulates the c‐Myc oncogenic expression. The peptide exhibits significant cytotoxic effect on cancer cells (HeLa and U2OS) compared to non‐cancer cells (HEK293) under similar experimental conditions. The study highlights the applicability of a synthetic bioactive peptide as a putative anticancer therapeutic. [ABSTRACT FROM AUTHOR]

The ability of a synthetic, aromatic tripeptide, H-Phe-Phe-Phe-OH (FFF) to recognize the double-stranded DNA (dsDNA) has been tested with various biophysical and thermodynamic techniques. From the study, it is established that the peptide can recognize the groove of the ct-DNA and the binding constant value calculated from the isothermal titration calorimetric (ITC) study at 25C is 9.96 × 10³ M-1. From ITC data it is also noticed that the peptide-DNA complexation is favored by positive standard molar entropy contribution (TΔS°) of 13.65 kJ mol-1 and negative standard molar enthalpy contribution (ΔH°) of -9.170 kJ mol-1. The temperature-dependent ITC study also shows that the equilibrium constant value decreases gradually with increasing temperature. However, the standard molar Gibbs energy change exhibits only minor alterations suggesting the occurrence of enthalpy-entropy compensation. The studies reveal the insight into the spectroscopic and thermodynamic prospect of the FFFct-DNA interaction in vitro and hold the promise of future applications as DNA targeting drug. [ABSTRACT FROM AUTHOR]