Carboranyl Oligonucleotides. 3. Biochemical Properties of Oligonucleotides Containing 5-(o-Carboranyl-1-yl)-2‘-deoxyuridine

• Published in: Biochemistry (Easton) 1996-05, Vol.35 (18), p.5741-5746
• Main Authors: Lesnikowski, Zbigniew J, Fulcrand, Géraldine, Lloyd, Robert M, Juodawlkis, Amy, Schinazi, Raymond F
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; Base Sequence; Boron Compounds - chemistry; Cattle; Deoxyuridine - analogs & derivatives; Deoxyuridine - chemistry; DNA Primers; Enzyme Induction; Exonucleases - metabolism; Exoribonucleases - biosynthesis; Humans; In Vitro Techniques; Molecular Sequence Data; Molecular Structure; Oligonucleotides - chemical synthesis; Oligonucleotides - chemistry; Oligonucleotides - metabolism; Polynucleotide 5'-Hydroxyl-Kinase - metabolism; Substrate Specificity
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi953078e

Boronated oligonucleotides are potential candidates for boron neutron capture therapy, antisense technology, and as tools in molecular biology. The biological properties of dodecathymidylic acids containing one or more 5-(o-carboran-1-yl)-2‘-deoxyuridine residues at different locations within the oligonucleotide chain were studied. 5-(o-Carboran-1-yl)-2‘-deoxyuridine containing oligonucleotides manifested marked increased lipophilicity and resistance to 3‘- or 5‘-phosphodiesterases compared to the corresponding unmodified oligomer. They were substrates for T4 polynucleotide kinase and primers for Escherichia coli polymerase I and human immunodeficiency virus type 1 reverse transcriptase but not for human DNA polymerase α and β. They also formed heteroduplexes 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.