Synthesis of 2,4,5-Triaminocyclohexane Carboxylic Acid as a Novel 2-Deoxystreptamine Mimetic

• Main Author: Roberts, Sarah Elizabeth
• Format: Others
• Published: BYU ScholarsArchive 2009
• Subjects: RNA; drug target; 2-deoxystreptamine; aminoglycoside; unnatural amino acid; structure-based rational design; fluorescence assay; Biochemistry; Chemistry
• Online Access: https://scholarsarchive.byu.edu/etd/2091; https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=3090&context=etd

RNAs have become increasingly recognized as possible drug targets due to their involvement in important biochemical functions, as well as their unique but well-defined structures. Recently published crystal structures depict the binding of a series of aminoglycosides- or more specifically- 2-deoxystretamine (2-DOS), the most preserved central scaffold of aminoglycosides, to a conserved 5'-GU-3'region on their target RNAs. A novel unnatural γ-amino acid, 1, has been synthesized using 2-deoxystreptamine as a template through structure-based rational design. The unnatural amino acid has been designed to replace a glycosidic linkage with an amide bond, which may limit the promiscuous binding characteristics of aminoglycosides through increased rigidity of the ligands and additional hydrogen bonding. The binding selectivity and affinity will be studied in the future through a fluorescence assay.