Studies on the biosynthesis of prenylated indole secondary metabolites from Aspergillus versicolor and Aspergillus sp.; and A novel approach to tumor specific drug delivery: use of a naphthyridine drug linker with a DNA hairpin
Date
2011
Authors
Finefield, Jennifer M., author
Williams, Robert Michael, advisor
Rovis, Tomislav, 1968-, committee member
Kennan, Alan J., committee member
Elliott, C. Michael, committee member
Thamm, Douglas H., committee member
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Abstract
Herein are documented our efforts in two projects, beginning with studies toward elucidating the biosynthesis of prenylated indole alkaloids from two different Aspergillus species. Marine-derived Aspergillus sp. and terrestrial-derived Aspergillus versicolor were found to produce antipodal metabolites, in which we have developed several putative biosynthetic pathways to determine the enantio-diverging point of these fungal cultures. Through the synthesis of several potential intermediates, both with and without isotopic labeling, as well as through bioinformatics analysis of both the (-)- and (+)-notoamide biosynthetic gene clusters, significant progress has been made toward identifying a single biosynthetic precursor that serves as an intermediate to the postulated enantio-diverging event, the intramolecular hetero Diels-Alder cycloaddition. In the second project discussed, through collaboration with Dr. James Berenson at the University of California, Los Angeles, we have developed a novel tumor specific drug delivery system. Two naphthyridine-drug derivatives were synthesized and conjugated to a modified DNA oligonucleotide specifically targeted for multiple myeloma cells. The oligonucleotide-drug conjugate was successfully delivered and activated specifically within RMI8226 multiple myeloma cells.
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Subject
naphthyridine
Aspergillus