MACROCYCLIC METAL-COMPLEXES FOR SELECTIVE RECOGNITION OF NUCLEIC-ACIDBASES AND MANIPULATION OF GENE-EXPRESSION

Interaction of Zn-II-cyclen complexes 1, 3, 6, and 7 with uracil and t hymine bases in double-stranded poly(A).poly(U) and poly(dA).poly(dT) has been investigated. These zinc(II) complexes lowered the melting te mperatures (T-m) of poly(A).poly(U) and poly(dA).poly(dT) in 5 mM Tris -HCl buffer (pH 7.6) containing 10 mM NaCl as their concentrations inc reased, indicating that they destabilized the duplex structure of poly nucleotides. The comparison of circular dichroism (CD) spectra of poly (A).poly(U), poly(A), and poly(U) in the presence of zinc(II) complex 3 led us to conclude that the spectral changes of poly(A).poly(U) were due to a structural change from double to single-strand, caused by zi nc(II) complex 3 binding exclusively to uracils in poly(U). The destab ilization effect of zinc(II) complexes was not observed with poly(dG). poly(dC) in thermal denaturation experiments (50% formamide aqueous so lution, 2.5 mM Tris-HCl buffer (pH 7.6) and 5 mM NaCl). However, the a cridine-pendant cyclen complex 3, which associates with guanine at N-7 and O-6, and through pi-pi stacking, interacted with poly(dG) in the double helix and greatly stabilized the poly(dG).poly(dC) double-stran d, as was indicated by the higher T-m than those with reference interc alating agents. Poly(A).poly(U) double-strand was most effectively dis rupted with a bis(Zn-II-cyclen) bridged by para-xylyl group 6 that was designed as a host molecule to bind to two neighboring uracils in a 1 :2 complex. Zn-II-cyclen complexes thus may become a prototype of smal l molecules that can affect the biological properties of nucleic acids at the molecular level.