Synthesis of pyrrolidinone PNA: A novel conformationally restricted PNA analogue

To preorganize PNA for duplex formation, a new cyclic pyrrolidinone PNA ana logue has been designed. In this analogue the aminoethylglycine backbone an d the methylenecarbonyl linker are connected, introducing two chiral center s compared to PNA. The four stereoisomers of the adenine analogue were synt hesized, and the hybridization properties of PNA decamers containing one an alogue were measured against complementary DNA, RNA, and PNA strands. The ( 3S,5R) isomer was shown to have the highest affinity toward RNA, and to rec ognize RNA and PNA better than DNA. The (3S,5R) isomer was used to prepare a fully modified decamer which bound to rU(10) with only a small decrease i n T-m(DeltaT(m)/mod = 1 degreesC) relative to aminoethylglycine PNA.