Synthesis of Fmoc-Protected (S,S)-trans-Cyclopentane Diamine Monomers Enables the Preparation and Study of Conformationally Restricted Peptide Nucleic Acids

An efficient synthesis of Fmoc-protected (S,S)-trans-cyclopentane PNA (tcypPNA) monomers starting from mono-Boc-protected (S,S)-1,2-cyclopentanediamine is reported. A general synthetic strategy was developed so that tcypPNA monomers with each nucleobase can be made in sufficient quantity and purity for use in solid-phase peptide synthesis (SPPS). The newly synthesized monomers were then successfully incorporated into 10-residue PNA oligomers using standard Fmoc chemistry for SPPS. The different tcypPNAs allow different positions in the sequence to be conformationally constrained with (S,S)-trans-cyclopentane to determine the effects on binding to complementary DNA.