Reference type: Thesis
Author:
Finefield, Jennifer M.
Year published: 2011
Full title:
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
Place published:
Colorado State University
Publisher:
Colorado State University
ISBN/ISSN: 9781124890388
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.
URL: http://search.proquest.com/pqdt/docview/896616940/abstract/13AC62297932A47EE48/14?accountid=12253
Category:
Health and environmental sciences, Pure sciences, Prenylated indole secondary metabolites, Aspergillus versicolor, Tumor specific drug delivery, Naphthyridine, DNA hairpin