Troger's base scaffold in racemic and chiral fashion as a spacer for bisdistamycin formation. Synthesis and DNA binding study
Head-to-head' oligo-N-methylpyrrole peptide dimers linked by a methano[1,5]diazocin scaffold are presented in racemic as well as chiral fashion. Their DNA binding activities were assayed on calf thymus DNA, poly(dA-dT)(2), and poly(dC-dG)(2) by NMR and ECD spectroscopies, and fluorescence probe displacement assay. The presented dimers prefer AT sequences, but show higher affinity to poly(dC-dG)(2) than distamycin A. The (4R,9R) configuration of methanodiazocin bridge was found to be better suited for interaction with ct-DNA and poly(dA-dT)(2) than (4S,9S) configuration. (c) 2006 Elsevier Ltd. All rights reserved.