CARBORANYL OLIGONUCLEOTIDES .3. BIOCHEMICAL-PROPERTIES OF OLIGONUCLEOTIDES CONTAINING 5-(O-CARBORANYL-1-YL)-2'-DEOXYURIDINE

Boronated oligonucleotides are potential candidates for boron neutron capture therapy, antisense technology, and as tools in molecular biolo gy. The biological properties of dodecathymidylic acids containing one or more 5-(o-carboran-1-yl)-2'-deoxyuridine residues at different loc ations within the oligonucleotide chain were studied. 5-(o-Carboran-1- yl)-2'-deoxyuridine containing oligonucleotides manifested marked incr eased lipophilicity and resistance to 3'- or 5'-phosphodiesterases com pared to the corresponding unmodified oligomer. They were substrates f or T4 polynucleotide kinase and primers for Escherichia coli polymeras e I and human immunodeficiency virus type 1 reverse transcriptase but not for human DNA polymerase alpha and beta. They also formed heterodu plexes that were substrates for E. coli RNase H, an essential property for antisense technology. These studies indicate that the carboranyl- containing oligonucleotides have desirable properties that need to be exploited further in the design of novel biopharmaceuticals.