In order to detect the biological activity of new synthetic short chain oligoamides, the present work gives the results of studies on the interaction between calf thymus DNA and short chain oligoamides: PyPyPy-gamma-Dp (ligand 1) and PyPyPyPy-gamma-Dp (ligand 2). In the circular dichroism (CD) spectra of the mixing solution of DNA with ligands a specific peak appears in the region of 300-380 nm wavelength, which indicates that both ligands I and 2 can bind calf thymus DNA specifically. H-1 NMR spectra show that aromatic ring protons of ligand I appear as an obvious down-field shift, while those protons in ligand 2 disappear since ligand 2 owns a higher binding affinity with DNA than that of ligand 1. Investigations of DNA transition by differential scanning calorimetry (DSC) reveal that DNA melting temperature rises due to binding with ligands, and that ligand 2 alters the DNA transition process more significantly. At the same time, the molar binding enthalpies of ligands with DNA are measured at 293 K. The difference between the binding affinity of ligand I and 2 with DNA implies that increasing the number of N-methylpyrrole increases both the binding site size and the binding affinity.