SYNTHESIS AND PROPERTIES OF AN OLIGONUCLEOTIDE MODIFIED WITH AN ACRIDINE DERIVATIVE AT THE ARTIFICIAL ABASIC SITE

The synthesis of an oligodeoxynucleotide (ODN) modified with 2-methoxy -6-chloro-9-aminoacridine (Acr) at an abasic site is described. A ster eochemically defined aminodiol, L-threoninol, was used to serve as art ificial abasic nucleoside. The molecule was modified so as to be suita ble for the standard phosphoramidite method and was incorporated into the interior of an ODN. In addition, N-hydroxysuccinimidyl -[9-(6-chlo ro-2-methoxy)acridinyl]-6-aminocaproate has been synthesized for posts ynthetic modification of the amino substrate of the L-threoninol moiet y in the ODN. By using absorption spectroscopy, it is shown that oligo (dA) conjugated with acridine binds with complementary strand in a 1:1 ratio. The melting temperature showed that the nonmodified (abasic) d uplex is destabilized as a result of lacking in base at the abasic sit e, but the covalently linked acridine ring compensates for the destabi lization effect. The fluorescence quantum yield of the acridine ring w as enhanced by connection to oligo(dA) and, further, by formation of a double-strand with the complementary ODN. The quantum yield is larger than that of intermolecular intercalation. The excitation spectra of Acr-ODN in the duplex is quite similar to the absorption spectra. The results indicate that the covalently linked acridine ring is selective ly intercalated into the adjacent abasic site.