OLIGO-ALPHA-THYMIDYLATES COVALENTLY-LINKED TO INTERCALATING AGENTS - CIRCULAR-DICHROISM STUDIES OF THEIR INTERACTION WITH COMPLEMENTARY SEQUENCES

The interaction between oligo-alpha-thymidylates covalently linked to an intercalating agent (an acridine derivative) and their complementar y sequences containing beta-nucleosides (poly(rA), poly(dA), r(Ap)7rA, p(dA)8) has been studied using circular dichroism spectroscopy. Bindi ng to poly(rA) and to poly(dA) of the modified oligonucleotides led to large changes in the induced circular dichroism signal of the acridin e ring. These changes depend on whether the dye is linked to the 3'- o r to the 5'-end of the oligonucleotide. Interaction with poly(rA) as w ell as interaction with an octadeoxyriboadenylate led to the formation of a 1A:1T complex. With poly(dA), in addition to the 1A:1T complex, a 1A:2T complex was observed when the acridine derivative was linked t o the 3'-end of the octa-alpha-thymidylate. The double-stranded struct ures formed with poly(rA) and poly(dA) were characterized by different environments of the acridine dye. Binding to poly(rA) gave much stron ger complexes than binding to poly(dA). With poly(rA) the complex was more stable when the dye was bound at the 5'-end of the oligonucleotid e. Comparison between the circular dichroism changes observed upon bin ding at the level of polymers [poly(rA) or poly(dA)] and those obtaine d at the level of oligomers [r(Ap)7rA or pd(A)8] gave information rela tive to the position of the acridine ring in the helix.