Promotion of Single-Strand Invasion of PNA to Double-Stranded DNA by Pseudo-Complementary Base Pairing

Canonical peptide nucleic acid (PNA), in which naturally occurring nucleobases (A, G, C, and T) are bound to a poly(N-(2-aminoethyl)glycine) backbone, forms a stable duplex with single-stranded complementary DNA. However, this PNA hardly forms stable complexes with double-stranded DNA. We here show that, when some of the A and T groups therein are replaced with pseudo-complementary nucleobases (2,6-diaminopurine and 2-thiouracil), even only one strand of this partially pseudo-complementary PNA efficiently invades double-stranded DNA. This single-strand invasion spontaneously occurs at 25–50 °C, indicating its promising applicability to versatile purposes both in vivo and in vitro. The promotion by 2,6-diaminopurine is primarily attributed to the formation of an additional hydrogen bond with T in one of the two DNA strands, whereas the 2-S atom in 2-thiouracil promotes stacking interactions with adjacent nucleobases. Furthermore, the present new methodology is successfully employed to site-selective scissi...