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Address: 300 PHAR
Phone: (319) 335-6652
Mentor: Kevin Rice, PhD
Undergraduate Institution: So. Illinois University, BA
Year Entered Into Program: 2008-2013
Cysteine-flanked, acridinylated peptides are currently being synthesized for prospective use in non-viral gene delivery. Acridine is installed on the side chain of lysine residues to promote intercalation between DNA base pairs, and cysteine-flanking provides a polymerization feature to the peptide via disulfide bonding, which should increase the affinity of the overall polymer for DNA. The disulfide bonds also provide a reversible means of attachment. Once inside the cell, the reductive environment should reduce the disulfide bonding and, in turn, decrease the affinity of the polymer for DNA. If polymerization is successful for these attachment peptides, one can envision the use of cysteine-flanked components of a complete delivery vector being reversibly polymerized and attached to DNA. While polydispersity may prove to be an issue in this process, further studies will be conducted to sequentially attach fragments via deprotection of cysteine with thiol-specific functional groups and subsequent disulfide linkage. This will most likely be accomplished in solid-phase beginning with one terminal peptide of the prospective polymer covalently attached to resin.
Fernandez, C.A., Baumhover, N.J., Duskey, J.T., Khargharia, S., Kizzire, K., Ericson, M.D., Rice, K.G.: Metabolically stabilized long-circulating PEGylated polyacridine peptide polyplexes mediate hydrodynamically stimulated gene expression in liver. Gene Therapy 18:23-37, 2011. PMCID: PMC2990782
Kizzire, K., Khargharia, S., Rice, K.G.: High-Affinity PEGylated Polyacridine Polyplexes Mediate Potent In Vivo Gene Expression. Gene Therapy. 20(4):407-416, 2013. PMCID: PMC3665005
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