Date of Award

12-2010

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Chemistry

Advisor

Arya, Dev P

Committee Member

Smith , Dennis

Committee Member

Creager , Stephen

Committee Member

Petty , Jeffrey

Abstract

Neomycin is an aminoglycoside antibiotic known for its high affinity for RNA duplex structures. Recent developments from our labs have indicated that aminoglycoside binding is not limited to RNA, but to nucleic acids that, like RNA, adopt conformations similar to A-form. Our group sought to further expand the utility of aminoglycoside binding to B-DNA structures by conjugating neomycin, an aminoglycoside antibiotic, with the B-DNA minor groove binding ligand Hoechst 33258. Envisioning a dual groove-binding mode, we have extended the potential recognition process to include a third, intercalative moiety. Furthermore, we observe remarkable recognition of such conjugates with RNA duplex. Spectroscopic studies such as UV melting, differential scanning calorimetry, isothermal fluorescence titrations, and circular dichroism together illustrate the multi-recognition properties of the novel neomycin-based conjugates.

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