SELECTIVE BINDING TO POLYNUCLEOTIDES OF THE HYBRID INTERCALATING GROOVE BINDER BIS(PYRROLECARBOXAMIDE)-OXAZOLOPYRIDOCARBAZOLE - A MOLECULARMODELING STUDY

In order to further characterize the binding of the hybrid molecule Ne tOPC [bis(pyrrolecarboxamide)-oxazolopyridocarbazole conjugate] to dou ble-stranded DNA, we have performed a molecular modeling study to inve stigate the binding modes of the complexes possibly formed between Net OPC and synthetic polynucleotides poly [(dA-dT)](2), poly [(dA).(dT)], and poly [d(G-C)](2) and interpreted the results in the light of the experimentally determined binding parameters. In agreement with experi mental data, the modeling study suggests that whatever was the binding mode of the complex formed, the complexation energy is markedly lower (thus favorable) for AT-containing polynucleotides than for poly d[(G -C)](2). With both poly [d(A).d(T)] and poly [d(A-T)](2), the most ene rgetically favored complex has netropsin and OPC moieties bound simult aneously in the minor groove of DNA. The second favored complex exhibi ts the bimodal binding, i.e., intercalation of OPC and minor groove bi nding of the netropsin moiety. For both types of complex, the energy o f complex formation is slightly lower with poly [d(A).d(T)]. The bindi ng site sizes of the modeled complexes are about seven and four base p airs to the full groove and bimodal binding, respectively.