Organometallic B12-DNA conjugate: synthesis, structure analysis, and studies of binding to human B12-transporter proteins
| Autor: | Miriam Hunger, Barbara Enders, Alexander Rieder, Elena Mutti, Bernhard Kräutler, Ebba Nexo |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Magnetic Resonance Spectroscopy
Haptocorrin Molecular Conformation Oligonucleotides Catalysis chemistry.chemical_compound Oligonucleotide polycyclic compounds Moiety Animals Humans chemistry.chemical_classification Drug Carriers Transcobalamins Intrinsic factor Chemistry Organic Chemistry nutritional and metabolic diseases General Chemistry Vitamins DNA Cobalamin Vitamin B 12 Biochemistry Oligodeoxyribonucleotides Drug delivery Glycoprotein Conjugate Protein Binding |
| Zdroj: | Hunger, M, Mutti, E, Rieder, A, Enders, B, Nexo, E & Kräutler, B 2014, ' Organometallic B12-DNA conjugate : synthesis, structure analysis, and studies of binding to human B12-transporter proteins ', Chemistry, vol. 20, no. 41, pp. 13103-7 . https://doi.org/10.1002/chem.201404359 |
| ISSN: | 1521-3765 |
| DOI: | 10.1002/chem.201404359 |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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