Hybridization between Oxy-Peptide Nucleic Acids and DNAs:  Dependence of Hybrid Stabilities on the Chain-Lengths, Types of Base Pairs, and the Chain Directions

Abstract

Oxy-peptide nucleic acids (OPNAs) of [-NH-CH(CH2-CH2-Base)-CH2-O-CH2-CO-]-type main chain with four different types of nucleobases (Base = A, G, C, and U) or with an abasic side group (X) were synthesized. Melting curves of the 1:1 hybrids of o(A(n))-d(Tn)) pairs with n = 6, 9, 12, and 15 showed very sharp transitions at high Tm values, particularly for long chains, indicating that nearly optimum matching is attained in the structure of the o(A(n))-d(Tn) hybrids. Effect of different types of base pairs on the hybrid stabilities was examined for the o(A4NA4)-d(T4N'T4) 1:1 mixtures where N is A, G, C, U, or X and N' is A, G, C, or T. In all series of the hybrids the complementary pairs showed the highest Tm values. The Tm values of the complementary pairs were about 35 degrees C when purine bases were inserted as the N group in the OPNA, but they were 20-23 degrees C when pyrimidine bases were inserted. The melting curves of the hybrids with a single mismatch were similar to those with a single X-N' pair, suggesting that the mismatch base pairs have been ignored in the hybrids. All complementary OPNA-DNA hybrids showed higher Tm values and sharper transitions than the corresponding DNA-DNA hybrids. The OPNA-DNA hybrids favor a parallel direction i.e., the N-terminal of OPNA is directed to the 5'-terminal of DNA.