Synthesis and-binding properties of pyrrolidinyl peptide nucleic acids bearing (1S,2S)-2-aminocyclopentane carboxylic acids space

Abstract

A solid phase protocol for the synthesis of a new peptide nucleic acid (PNA) carring all four nucleobases has been developed. The PNA monomers in this research consist of a nucleobase-modified pyrrolidine derivatives with cis-D stereochemistry and (1S,2S)-2-aminocyclopentanecarboxylic acid (ACPC). The optimized solid phase synthesis conditions include the use of Pfp-activated monomer with HOAt and DIEA for 30 minutes in the coupling step. For capping step, lauroyl chloride and DIEA were used in order to facilitate the purification of PNA. The average coupling yield in each step was generally over 95 %. A number of mixed bases PNA with 5-15 mer in length were successfully synthesized by this protocol. Tm studies with complementary DNA showed that the PNA can form a stable hybrid with high affinity and sequence specificity for Watson-Crick type base pairing (A-T, C-G) exclusively in an antiparallel fashion. These PNA also exhibited a strong preference for binding to DNA over RNA and over self pairing.