Sequence specific conjugates of minor groove ligands with inosine containing oligodeoxyribonucleotides

: Conjugates of the distamycin tetrapyrrole analogue containing four pyrrolecaboxamide fragments (MGB) with inosine-containing oligodeoxyribonucleotides were synthesized. The stability of duplexes formed by these conjugates depends on the composition of inosine-containing pairs and decreases in the order: IC > IA > > IT. For the duplexes (d(TTTATATA)p(MGB))2, (d(TTCICICI)p(MGB))2, and (d(TTAIAIAI)p(MGB))2, the melting temperatures are 68, 54, and 35-45 degrees C, respectively; (d(TTTITITI)p(MGB))2 forms no duplexes at temperatures above 4 degrees C. The binding was shown to be highly specific: in the duplex d(GGCATCTA)p(MGB).d(GGTAIATI)p(MGB), the substitution of only one A.T pair by A.A decreases the binding constant by almost three orders of magnitude.