Effect of intercalator substituent and nucleotide sequence on the stability of DNA- and RNA-naphthalimide complexes.

摘要: DNA intercalators are commonly used as anti-cancer and anti-tumor agents. As a result, it is imperative to understand how changes in intercalator structure affect binding affinity DNA. Amonafide mitonafide, two naphthalimide derivatives that active against HeLa KB cells vitro, were previously shown intercalate into Here, systematic study was undertaken change the 3-substituent on aromatic 1,8-naphthalimide determine 11 different functional groups with variety of physical electronic properties RNA duplexes sequence compositions lengths. Wavelength scans, NMR titrations, circular dichroism investigate mode short synthetic Optical melting experiments measure temperature due intercalation, which ranged from 0 19.4°C. Thermal stabilities affected by changing substituent, several patterns idiosyncrasies identified. By systematically varying 3-substituent, strength same derivative various compared. The sequences also results these comparisons shed light complexities site specificity DNA-intercalator complexes. For example, consequences adding 5'-TpG-3' or 5'-GpT-3' step duplex dependent composition duplex. When added poly-AT duplex, enhanced 5.6-11.5°C, but when poly-GC diminished 3.2-6.9°C.