Development and characterization of a new class of metalchelating nucleic acids
Abstract
Antisense technology is a promising new route to the development of highly specific drugs with broad applicability and low side effects. The efficacy of standard oligodeoxyribonucleotides as antisense therapeutics is limited by susceptibility to exo- and endo-nucleases and poor cellular uptake. To overcome these obstacles to the use of antisense technology as a general therapeutic, numerous alterations have been made to the structure of oligodeoxynucleotides. To permit the introduction of the unique properties by addition of metal-complexes to nucleic acid structures, we have designed a series of oligodeoxyribonucleotides in which metal-chelating species serve as replacements for single nucleosides. These ligand nucleosides, bipyridine, piperazine, or dithioether, can be incorporated into oligodeoxynucleotides via standard solid phase techniques. These metal-chelating nucleic acids bind unmodified complements with high affinity in the presence of certain metal ions. Metal-ligand binding is responsible for the observed enhancement of duplex stability as indicated by fluorescence quenching assays and control thermal stability studies.
Degree
Ph.D.
Advisors
Wilker, Purdue University.
Subject Area
Biochemistry|Inorganic chemistry|Organic chemistry
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