The effects of varying the substituent and DNA sequence on the stability of 4-substituted DNA-naphthalimide complexes

Abstract

DNA duplexes are stabilized by many interactions, one of which is stacking interactions between the nucleic acid bases. These interactions are useful for designing small molecules that bind to DNA. Naphthalimide intercalators have been shown to be valuable anti-cancer agents that stack between the DNA bases and exhibit stabilizing effects. There is a continued need to design intercalators that will exhibit these stabilizing effects while being more selective toward DNA binding. This work investigates 4-substituted naphthalimides with varying functional groups and their interactions with nucleic acid duplexes. Mode of binding was determined via wavelength scans, circular dichroism, and viscosity measurements. Optical melting experiments were used to measure the absorbance of the sample as a function of temperature. The Tm values derived from the DNA duplexes were subtracted from the Tm values derived from the DNA-intercalator complexes, resulting in ΔTm values. The ΔTm values demonstrated that the substituents on the intercalator affect the stability of the DNA-intercalator complex. From the results of this study and comparison to results from previous work, we conclude that the substituent type and position on the core intercalator molecule affect the stability of the complex it forms with DNA.