title: Carboranyl oligonucleotides: 4. synthesis and physicochemical studies of oligonucleotides containing 2'-O-(o-carboran-1-yl)methyl group.
abstract: Boronated oligonucleotides are potential candidates for antisense oligonucleotide technology (AOT), boron neutron capture therapy (BNCT), and as tools in molecular biology. A method was developed for the solid phase synthesis of oligonucleotides containing 2'-O-(o-carboran-1-yl-methyl) (2'-CBM) group. Synthesis was performed using a standard beta-cyanoethyl cycle and automated DNA synthesizer. Manual steps were performed for the insertion of a modified monomer bearing the 2'-CBM group. Several tetradecanucleotides complementary to DNA-HCMV, and bearing 2'-CBM modification near the 3'-end or 5'-end or in the middle of the oligonucleotide chain were synthesized. The resulting oligomers were characterized by polyacrylamide gel electrophoresis (PAGE), reverse phase high-performance liquid chromatography (RP-HPLC), matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and ultraviolet spectroscopy (UV), circular dichroism (CD), and melting temperature (Tm) measurements. Tm of duplexes formed between 2'-CBM-modified tetradecanucleotides and complementary DNA and RNA template were compared with those formed by the unmodified oligonucleotide and complementary sequence. The stability of 2'-CBM oligonucleotides in the presence of phosphodiesterase I from Crotalus atrox venom and in human serum was studied. Oligonucleotides bearing the 2'-CBM group are characterized by increased resistance to enzymatic digestion, increased lipophilicity, and the ability to form stable duplexes with complementary templates.
authors.affiliation: Laboratory of Molecular Virology and Biological Chemistry, Center of Microbiology and Virology, Polish Academy of Sciences, Lodz.
authors.forename: Agnieszka B
authors.initials: AB
authors.lastname: Olejniczak
authors.forename: Maria
authors.initials: M
authors.lastname: Koziolkiewicz
authors.forename: Zbigniew J
authors.initials: ZJ
authors.lastname: Lesnikowski
mesh_terms: D000818:Animals; D001483:Base Sequence; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003587:Cytomegalovirus / Q000235:genetics; D004355:Drug Stability; D005092:Exonucleases / Q000097:blood; D005814:Genes, Viral; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D009369:Neoplasms / Q000628:therapy; D020319:Oligodeoxyribonucleotides, Antisense / Q000138:chemical synthesis* / Q000737:chemistry* / Q000235:genetics / Q000627:therapeutic use; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism
chemical_list: D001896:Boron Compounds; D020319:Oligodeoxyribonucleotides, Antisense; D005092:Exonucleases; C022650:spleen exonuclease; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I