Kinetic Recognition of AT-Rich DNA by Ruthenium Complexes

摘要

DNA recognition, in nature as well as gene-targeting technology, is generally based on thermodynamically controlled equilibrium binding. In the classical lock-and-key model, the DNA nucleobases, in close contact with the bound drug, determine the binding affinity, which limits selectivity to short sequences for small drug molecules. Herein we report that a high selectivity for long AT stretches can be attained through kinetically controlled DNA intercalation by binuclear ruthenium(II) complexes. The number of adjacent A-T base pairs is a decisive factor for the intercalation rate that is found to vary more than three orders of magnitude between mixed-sequence and alternating AT-sequence DNA. We speculate that this principle of kinetic recognition may be used by nature in nucleic acid biology. More specifically, kinetic recognition can be exploited to direct drugs to DNA targets characterized by long AT stretches in a highly selective manner.