Insertion of an internal dipeptide into PNA oligomers: thermal melting studies and further functionalization

The solid phase synthesis of PNA oligomers with the internal dipeptide Gly-Phe is presented and the interaction with complementary DNA investigated. UV absorbance melting experiments with different but complementary DNA sequences show that stable PNA x DNA duplexes are only obtained when there is no DNA base opposite the dipeptide unit. Instead, the dipeptide spacer forms a loop-like structure within the duplex. Further functionalization with N-heterocyclic ligands is described. p-Nitro-phenylalanine is introduced in place of Phe during solid phase synthesis and subsequently reduced to p-amino-phenylalanine. Reaction with activated acids provides the ligand conjugates in high yield and purity. This strategy opens a universal route to a large number of internal substitutions in PNA chemistry.