Abstract: A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. Methods of increasing binding affinity and sequence specificity of peptide nucleic acids are provided wherein some peptide nucleic acids comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone, while other peptide nucleic acids contain at least one 2,6-diaminopurine nucleobase and at least one C.sub.1 -C.sub.8 alkylamine side chain.