title: Carboranyl oligonucleotides. 3. Biochemical properties of oligonucleotides containing 5-(o-carboranyl-1-yl)-2'-deoxyuridine.
abstract: 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 alpha and beta. 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.
authors.affiliation: Veterans Affairs Medical Center, Decatur, Georgia 30033-4004, USA.
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Lesnikowski
authors.forename: G
authors.initials: G
authors.lastname: Fulcrand
authors.forename: R M
authors.initials: RM
authors.lastname: Lloyd
authors.forename: A
authors.initials: A
authors.lastname: Juodawlkis
authors.forename: R F
authors.initials: RF
authors.lastname: Schinazi
mesh_terms: D000818:Animals; D001483:Base Sequence; D001896:Boron Compounds / Q000737:chemistry; D002417:Cattle; D017931:DNA Primers; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000737:chemistry; D004790:Enzyme Induction; D005092:Exonucleases / Q000378:metabolism; D005095:Exoribonucleases / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011116:Polynucleotide 5'-Hydroxyl-Kinase / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D001896:Boron Compounds; D017931:DNA Primers; D009841:Oligonucleotides; C087057:5-carboranyl-2'-deoxyuridine; D011116:Polynucleotide 5'-Hydroxyl-Kinase; D005092:Exonucleases; D005095:Exoribonucleases; C022535:exoribonuclease II; C022650:spleen exonuclease; D003857:Deoxyuridine