Design, Synthesis, and Hybridisation of Water-Soluble, Peptoid Nucleic Acid Oligomers Tagged with Thymine

Abstract

The preparation of a new class of backbone-modified PNA mimetic incorporating thymine is described. Target dipeptoid monomer 21 was synthesised from an N-[2-(thymin-1-yl)ethyl] glycinate ester and a properly protected iminodiacetic acid. The distinctive structural motif in the backbone is a carboxy group, inserted to impart water solubility to the oligomer. Two achiral oligopeptoid sequences (8-mer and 12- mer), characterised by the shift of the amide carbonyl group away from the nucleobase, were efficiently assembled according to solid-phase synthesis protocols. Thermal denatur-ation studies showed that the two homopyrimidine oligopeptoids do not effectively hybridise with complementary sequences of DNA and RNA or fully synthetic (2,4-diamino)- triazin-6-yl-tagged peptoid 22. A possible reason could reside in the concurrent unfavourable influence of the anionic N-(carboxymethyl) moieties and the flexible nucleobase/ backbone ethylene linker