Expanding the repertoire of heterocycle ring pairs for programmable minor groove DNA recognition.
The discrimination of the four Watson-Crick base pairs by minor groove DNA-binding polyamides have been attributed to the specificity of three five-membered aromatic amino acid subunits, 1-methyl-1H-imidazole (Im), 1-methyl-1H-pyrrole (Py), and 3-hydroxy-1H-pyrrole (Hp) paired four different ways. The search for additional ring pairs that demonstrate DNA-sequence specificity has led us to a new class of 6-5 fused bicycle rings as minor groove recognition elements. The affinities and specificities of the hydroxybenzimidazole/pyrrole (Hz/Py) and hydroxybenzimidazole/benzimidazole (Hz/Bi) pairs for each of the respective Watson-Crick base pairs within the sequence context 5'-TGGXCA-3' (X = A, T, G, C) were measured by quantitative DNaseI footprinting titrations. The Hz/Py and Hz/Bi distinguish T.A from A.T. Hairpin polyamides containing multiple Hz/Py pairs were examined and were shown to mimic the Hp/Py pair with regard to affinity and specificity. Therefore, the Hz/Py pair may be considered a second-generation replacement for the Hp/Py pair.
Marques
Michael A
MA
Contribution from the Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Doss
Raymond M
RM
Foister
Shane
S
Dervan
Peter B
PB
D020029:Base Pairing; D001562:Benzimidazoles / Q000737:chemistry; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry*; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry*; D007191:Indazoles / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry*
D001562:Benzimidazoles; D007093:Imidazoles; D007191:Indazoles; D009757:Nylons; D011758:Pyrroles; C001373:hydroxybenzindazole; D004247:DNA; C031000:benzimidazole; D003850:Deoxyribonuclease I; C096654:N-methylpyrrole; C018100:1-methylimidazole