Backbone modifications of aromatic peptide nucleic acid (APNA ) monomers and their hybridization properties with DNA and RNA.
Aromatic peptide nucleic acid (APNA) monomers containing N-(2-aminobenzyl)-glycine, N-(2-aminobenzyl)-(R)- or -(S)-alanine, and N-(2-aminobenzyl)-beta-alanine moieties as part of their backbone were synthesized. These novel analogues were incorporated as a single "point mutation" in PNA hexamers, and their physicochemical properties were investigated by UV thermal denaturation and CD experiments. Destabilization in triplex formation between the PNA-APNA chimeras and complementary DNA or RNA oligomers was observed, as compared to the PNA control. The APNA monomer composed of the N-(2-aminobenzyl)-glycine backbone led to the smallest decrease in the thermal stability of the triplexes formed with DNA and RNA, while maintaining selectivity for base-pairing recognition. Since the PNA-APNA chimeras are more lipophilic than the corresponding PNA homopolymers, these oligomers may also exhibit better cell membrane permeability properties.
Fader
L D
LD
Department of Chemistry, McGill University, Montreal, Quebec H3A 2K6, Canada.
Boyd
M
M
Tsantrizos
Y S
YS
D000613:Aminobutyrates / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D001596:Benzylamines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D004355:Drug Stability; D006358:Hot Temperature; D009691:Nucleic Acid Denaturation; D009693:Nucleic Acid Hybridization; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011061:Poly A / Q000378:metabolism; D011119:Polynucleotides / Q000378:metabolism*; D013941:Thymine
D000613:Aminobutyrates; D001596:Benzylamines; D020135:Peptide Nucleic Acids; D011119:Polynucleotides; D011061:Poly A; C015465:poly(dA); C014328:2-amino-4-phenylbutyric acid; D013941:Thymine