Programmable oligomers for minor groove DNA recognition.
The four Watson-Crick base pairs of DNA can be distinguished in the minor groove by pairing side-by-side three five-membered aromatic carboxamides, imidazole (Im), pyrrole (Py), and hydroxypyrrole (Hp), four different ways. On the basis of the paradigm of unsymmetrical paired edges of aromatic rings for minor groove recognition, a second generation set of heterocycle pairs, imidazopyridine/pyrrole (Ip/Py) and hydroxybenzimidazole/pyrrole (Hz/Py), revealed that recognition elements not based on analogues of distamycin could be realized. A new set of end-cap heterocycle dimers, oxazole-hydroxybenzimidazole (No-Hz) and chlorothiophene-hydroxybenzimidazole (Ct-Hz), paired with Py-Py are shown to bind contiguous base pairs of DNA in the minor groove, specifically 5'-GT-3' and 5'-TT-3', with high affinity and selectivity. Utilizing this technology, we have developed a new class of oligomers for sequence-specific DNA minor groove recognition no longer based on the N-methyl pyrrole carboxamides of distamycin.
Doss
Raymond M
RM
The Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Marques
Michael A
MA
Foister
Shane
S
Chenoweth
David M
DM
Dervan
Peter B
PB
D020029:Base Pairing; D004247:DNA / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D009757:Nylons / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry*; D011485:Protein Binding; D011758:Pyrroles
D009757:Nylons; D009841:Oligonucleotides; D011758:Pyrroles; D004247:DNA