I am interested in the design of DNA binding ligands which are including DNA minor groove binders and G-quadruplex stabilizing agents. Certain natural products, distamycin and belomycin are considered as models for designing new DNA binding agents. A variety of DNA binding ligands were synthesized and accordingly characterized by different bioassays. In the series of azo-pyrrole-polyamide, it showed slight DNA binding affinity but has the properties of DNA photo-cleavage and recognition of mixed sequence. The thiophene series showed strong binding ability for duplex DNA. Bithiophene series showed a remarkable binding affinity to duplex DNA which is compatible to natural products netropsin and distamycin. The pyridodicarboxamide series remain intramolecular hydrogen bonding with poor preferences for duplexes DNA even though they stabilized quadruplex DNA. The bithiophene-bipyrimidine compound binds to specific hexanucleotide sequence 5¡¦-AAGCTT-3¡¦ and acts as an unfused quadruplex stabilization ligand. In the quinoline series, the combination of quinoline and methylpyrrole polyamide proves the attenuation effect for quadruplexes stabilization which provides a novel strategy for development of quadruplex binding logands. In this study, several series of small molecules for DNA binding have been successfully synthesized and proved to interact with DNA secondary structures according to the particular properties of themselves.