Published online 9 February 2005
Article |
Molecular recognition of DNA base pairs by the formamido/pyrrole and formamido/imidazole pairings in stacked polyamides
1 Department of Chemistry, Furman University Greenville, SC 29613, USA 2 Department of Chemistry, Georgia State University Atlanta, GA 30303, USA 3 Department of Chemistry and Biochemistry, University of Northern Colorado Greeley, CO 80639, USA
*To whom correspondence should be addressed. Tel: +1 864 294 3368; Fax: +1 864 294 3559; Email: moses.lee{at}furman.edu
Received November 30, 2004. Revised January 20, 2005. Accepted January 20, 2005.
Polyamides containing an N-terminal formamido (f) group bind to the minor groove of DNA as staggered, antiparallel dimers in a sequence-specific manner. The formamido group increases the affinity and binding site size, and it promotes the molecules to stack in a staggered fashion thereby pairing itself with either a pyrrole (Py) or an imidazole (Im). There has not been a systematic study on the DNA recognition properties of the f/Py and f/Im terminal pairings. These pairings were analyzed here in the context of f-ImPyPy, f-ImPyIm, f-PyPyPy and f-PyPyIm, which contain the central pairing modes, –ImPy– and –PyPy–. The specificity of these triamides towards symmetrical recognition sites allowed for the f/Py and f/Im terminal pairings to be directly compared by SPR, CD and 
T M experiments. The f/Py pairing, when placed next to the –ImPy– or –PyPy– central pairings, prefers A/T and T/A base pairs to G/C base pairs, suggesting that f/Py has similar DNA recognition specificity to Py/Py. With –ImPy– central pairings, f/Im prefers C/G base pairs (>10 times) to the other Watson–Crick base pairs; therefore, f/Im behaves like the Py/Im pair. However, the f/Im pairing is not selective for the C/G base pair when placed next to the –PyPy– central pairings.
Correspondence may also be addressed to W. David Wilson. Tel: +1 404 651 3903; Fax: +1 404 651 1416; Email: chewdw{at}panther.gsu.edu