Interactions of diastereomeric tripeptides of lysyl-5-fluorotryptophyllysine with DNA. 2. Optical, 19F NMR, and strand cleavage studies of apurinic DNA complexes.

The interactions of the diastereomers lysyl-5-fluoro-L-tryptophyllysine and lysyl-5-fluoro-D-tryptophyllysine with apurinic DNA have been examined as a model for the action of DNA repair enzymes. The binding characteristics of the tripeptide diastereomers to DNA, modified to contain approximately 5% apurinic sites, were studied by measuring 19F NMR parameters, fluorescence quenching, and activity in promoting single-strand cleavage of plasmid DNA. The affinities of each of the peptides to apurinic DNA are similar to those for native DNA. However, the 19F NMR chemical shift and relaxation behavior indicates that both diastereomers form complexes with apurinic DNA that are distinct from those formed with native DNA. In addition, the 19F NMR measurements differ for the L-Trp and D-Trp complexes with apurinic DNA. In spite of these differences, when either of the tripeptide diastereomers is incubated with plasmid DNA containing apurinic sites, no difference in the rate of single-strand cleavage of the DNA is detectable.