title: Organometallic B12-DNA conjugate: synthesis, structure analysis, and studies of binding to human B12-transporter proteins.
abstract: Design, synthesis, and structural characterization of a B12-octadecanucleotide are presented herein, a new organometallic B12-DNA conjugate. In such covalent conjugates, the natural B12 moiety may be a versatile vector for controlled in vivo delivery of oligonucleotides to cellular targets in humans and animals, through the endogenous B12 transport systems. Binding of the organometallic B12 octadecanucleotide to the three important human proteins of B12 transport was studied, to examine its structural suitability for the task of eventual in vivo oligonucleotide delivery. Binding was efficient with transcobalamin (TC), but not so efficient with the homologous glycoproteins intrinsic factor and haptocorrin. Binding of the B12 octadecanucleotide to TC suggests the capacity of the B12 moiety to serve as a natural vector for specific transport of single stranded, organometallic oligonucleotide loads from the blood stream into cells.
authors.affiliation: Institute of Organic Chemistry and Center for Molecular Biosciences (CMBI), Innrain 80/82, University of Innsbruck, 6020 Innsbruck (Austria).
authors.forename: Miriam
authors.initials: M
authors.lastname: Hunger
authors.forename: Elena
authors.initials: E
authors.lastname: Mutti
authors.forename: Alexander
authors.initials: A
authors.lastname: Rieder
authors.forename: Barbara
authors.initials: B
authors.lastname: Enders
authors.forename: Ebba
authors.initials: E
authors.lastname: Nexo
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kräutler
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry; D011485:Protein Binding; D014155:Transcobalamins / Q000737:chemistry* / Q000378:metabolism; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D014155:Transcobalamins; D004247:DNA; D014805:Vitamin B 12
keywords: DNA; cobalamin; drug delivery; oligonucleotide; vitamins