Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA.
The synthesis and DNA binding properties of bis-PNA (peptide nucleic acid) are reported. Two PNA segments each of seven nucleobases in length were connected in a continuous synthesis via a flexible linker composed of three 8-amino-3,6-dioxaoctanoic acid units. The sequence of the first strand was TCTCTTT (C- to N-terminal), while the second strand was TTTCTCT or TTTJTJT, where J is pseudoisocytosine. These bis-PNAs form triple-stranded complexes of somewhat higher thermal stability than monomeric PNA with complementary oligonucleotides and the thermal melting transition shows very little hysteresis. When the J base is placed in the strand parallel to the DNA complement ('Hoogsteen strand'), the DNA binding was pH independent. The bis-PNAs were also superior to monomeric PNAs for targeting double-stranded DNA by strand invasion.
Egholm
M
M
Department of Organic Chemistry, H.C. Orsted Institute, Universitetsparken 5, Copenhagen, Denmark.
Christensen
L
L
Dueholm
K L
KL
Buchardt
O
O
Coull
J
J
Nielsen
P E
PE
D001483:Base Sequence; D001665:Binding Sites; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004355:Drug Stability; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011196:Potassium Permanganate; D013329:Structure-Activity Relationship
D046911:Macromolecular Substances; C092077:N-(2-(tert-butyloxycarbonyl)aminoethyl)-N-(N2-(benzyloxycarbonyl)isocytosin-5-ylacetyl)glycine; D011196:Potassium Permanganate; D003596:Cytosine; D004247:DNA