A Novel N-(Pyrrolidinyl-2-methyl)glycine-Based PNA with a Strong Preference for RNA over DNA

Abstract

A novel, N-(pyrrolidinyl-2-methyl)glycine-based (Pmg-based) PNA is introduced. The synthesis of the backbone was accomplished in good yield, starting from prolinol. Thymine (S)- and (R)-Pmg and adenine- and cytosine-derived (R)-Pmg monomers were prepared. Five different fragments − two with either the (R) or the (S) isomer of the thymine Pmg monomer, two oligomers with two consecutive (R)- or (S)-thymine Pmg units, and fully modified (R)-Pmg decamer − were assembled on a solid support. UV thermal melting experiments with complementary DNA and RNA were performed in order to determine the effects of conformational restriction, steric hindrance, and chirality on the duplex stability. It was found that the (R)-Pmg-containing PNAs bound better to DNA and RNA than those containing the (S)-Pmg isomer and that both (S)- and (R)-Pmg-containing PNAs preferentially bound to complementary RNA with a selectivity higher than that of 2-(aminoethyl)glycine (Aeg) PNA. However, even (R)-Pmg-containing oligomers showed poorer duplex stability than nonmodified Aeg-PNA, while no detectable binding either to the DNA or to the RNA was observed with the fully modified (R)-Pmg decamer. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)