DNA structure control by polycationic species: Polyamine, cobalt ammines, and di-metallo transition metal chelates

Many polycationic species bind to DNA and induce structural changes. The wo rk reported here is the first phase of a program whose long-term aim is to create a class of simple and inexpensive sequence-selective compounds that will enable enhanced DNA structure control for a wide range of applications . Three classes of molecule have been included in this work: the polyamine spermine (charge: 4(+)) and spermidine (charge: 3(+)) (which are known to i nduce a wide range of DNA conformational changes but whose binding modes ar e still not well understood); cobalt (III) ammine transition metal complexe s as potential polyamine mimics and [Fe(H2O)(6)](3+); and the first member of a new class of di-metallo tris-chelated cylinders of helical structure ( charge 4(+)). Temperature-dependent absorption, circular dichroism, linear dichroism, gel electrophoresis, and molecular modeling data are presented. The cobalt ammines prove to be effective polyamine mimics, although their b inding appears to be restricted to backbone and major groove. All the ligan ds stabilize the DNA, but the 4(+) di-iron tris-chelate does so comparative ly weakly and seems to have a preference for single-stranded DNA. All the m olecules studied bend the DNA, with the di-iron tris-chelate having a parti cularly dramatic effect even at very low drug load. (C) 2000 Wiley-Liss, In c.