Open AccessBinding site size limit of the 2:1 pyrrole-imidazole polyamide-DNA motif.
Author(s) -
John J. Kelly,
E.E. Baird,
Peter B. Dervan
Publication year - 1996
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.14.6981
Subject(s) - antiparallel (mathematics) , polyamide , dna , minor groove , imidazole , chemistry , binding site , titration , ring size , stereochemistry , crystallography , biochemistry , ring (chemistry) , polymer chemistry , organic chemistry , physics , magnetic field , quantum mechanics
Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids can be combined in antiparallel side-by-side dimeric complexes for sequence-specific recognition in the minor groove of DNA. Six polyamides containing three to eight rings bind DNA sites 5-10 bp in length, respectively. Quantitative DNase I footprint titration experiments demonstrate that affinity maximizes and is similar at ring sizes of five, six, and seven. Sequence specificity decreases as the length of the polyamides increases beyond five rings. These results provide useful guidelines for the design of new polyamides that bind longer DNA sites with enhanced affinity and specificity.
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