Configurational preference of pyrrolidine-based oxy-peptide nucleic acids as hybridization counterparts with DNA and RNA.
A new series of oxy-peptide nucleic acids (pyrrolidine-based oxy-peptide nucleic acids = POPNAs) of four different stereoisomeric forms (cis-L, cis-D, trans-L, trans-D) have been synthesized. To find a favorable stereoisomer of POPNA for hybridization with DNA or RNA, thermodynamic parameters and conformations of the hybrids between the four stereoisomers with 9 adenine bases [po(A(9))s] and dT(9) or rU(9) were investigated from ultraviolet (UV) melting curves and circular dichroism (CD) spectra. The cis-L-po(A(9)) formed the most stable hybrid with dT(9), because of the smallest entropy loss, despite the smallest enthalpy gain. In contrast, trans-L-po(A(9)) formed the most stable hybrid with rU(9), because of the largest enthalpy gain, despite the largest entropy loss. The hybrid stability of trans-L-po(A(9)) with rU(9) was significantly improved as compared with a previous version of oxy-peptide nucleic acid (OPNA) that lacks the pyrrolidine ring.