STRUCTURE-ACTIVITY STUDIES OF THE BINDING OF MODIFIED PEPTIDE NUCLEIC-ACIDS (PNAS) TO DNA
Artikel i vetenskaplig tidskrift, 1994

Peptide nucleic acid (PNA) oligomers where one of the repeating backbone 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 PNA oligomers and complementary DNA oligonucleotides was significantly lower than that of the corresponding complexes involving unmodified PNA. However, the sequence selectivity was retained. Thymidyl decamers with all N-(2-aminoethyl)-beta-alanine or N-(3-aminopropyl)glycine backbones were prepared and shown to be unable to hybridize to the complementary (dA)(10) oligonucleotides, whereas a PNA decamer containing only ethylenecarbonyl linkers between the nucleobases and the N-(2-aminoethyl)glycine backbone showed weak but sequence-specific affinity for complementary DNA. All hybrids involving homopyrimidine PNA oligomers exhibited (PNA)(2)/DNA stoichiometry, whereas mixed-sequence PNA oligomers formed PNA/DNA duplexes. The preferred binding direction between the modified PNA and DNA in the duplex motifs was antiparallel, as previously reported for complexes involving unmodified PNA.

recognition

oligonucleotides

adenine

thymine

polyamide

cytosine

guanine

hybrids

Författare

B. Hyrup

M. Egholm

P. E. Nielsen

Pernilla Wittung Stafshede

Institutionen för fysikalisk kemi

Bengt Nordén

Institutionen för fysikalisk kemi

O. Buchardt

Journal of the American Chemical Society

0002-7863 (ISSN) 1520-5126 (eISSN)

Vol. 116 18 7964-7970

Ämneskategorier

Kemi

DOI

10.1021/ja00097a002