STRUCTURE-ACTIVITY STUDIES OF THE BINDING OF MODIFIED PEPTIDE NUCLEIC-ACIDS (PNAS) TO DNA

Peptide nucleic acid (PNA) oligomers where one of the repeating backbo ne units is extended with a methylene group to either N-(2-aminoethyl) -beta-alanine or N-(3-aminopropyl)glycine were prepared. Alternatively , the linker to the nucleobase was extended from methylenecarbonyl to ethylenecarbonyl. The thermal stability of the hybrids between these P NA oligomers and complementary DNA oligonucleotides was significantly lower than that of the corresponding complexes involving unmodified PN A. However, the sequence selectivity was retained. Thymidyl decamers w ith all N-(2-aminoethyl)-beta-alanine or N-(3-aminopropyl)glycine back bones were prepared and shown to be unable to hybridize to the complem entary (dA)(10) oligonucleotides, whereas a PNA decamer containing onl y ethylenecarbonyl linkers between the nucleobases and the N-(2-aminoe thyl)glycine backbone showed weak but sequence-specific affinity for c omplementary DNA. All hybrids involving homopyrimidine PNA oligomers e xhibited (PNA)(2)/DNA stoichiometry, whereas mixed-sequence PNA oligom ers formed PNA/DNA duplexes. The preferred binding direction between t he modified PNA and DNA in the duplex motifs was antiparallel, as prev iously reported for complexes involving unmodified PNA.