Conformational Analysis of Neomycin B and Its Derivative
Vanessa Rangel and Anoopjit Singh Kooner - Seniors. Amelia Watson - Third Year Ph.D.
31st Annual National Conference on Undergraduate Research
Council on Undergraduate Research
University of Memphis, Memphis, TN
April 6-8, 2017
Date of Presentation
Neomycin B is an aminoglycoside antibiotic, topically used to prevent and treat infections. When ingested, Neomycin cannot be absorbed by the intestine and therefore can be prescribed during liver failure or before GI surgery to keep ammonia levels and bacterial levels low and prevent hepatic encephalopathy, which is loss of brain function due to a buildup of toxins. Neomycin B binds to a specific protein in the bacterial ribosome and interferes with bacterial protein synthesis, which leads to destruction of the bacterium. In addition, neomycin B is known to bind to RNA as well as triple-strand-DNA. The exact location of binding in the latter case is not known and is subject to ongoing research in multiple groups. The effectiveness of binding (matched molecular “handshake” or “key-lock” match) is dependent on neomycin’s solution conformation. Even if new chemical structure is added to neomycin (“key chain”), neomycin’s structure (“key”) must remain unaltered to fit the binding site (“lock”). The objective of this project was to characterize the solution geometry of neomycin B and an EDTA-derivative thereof. To our knowledge, neomycin has not been fully characterized in recent years. Quantitative information about its conformation in solution and the effects of attached substituents on the structure guides scientists in deciphering neomycin’s mode of action. In the present work, complete conformational analysis was accomplished by nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations. We assigned all 1H-, 13C, and 15N-resonances unambiguously, confirmed by short- and long-distance correlations. Quantitative coupling constants and qualitative 1H-1H-distances were extracted from J-resolved HMBC and NOE experiments. The compounds 2-(hydroxymethyl)-tetrahydrofuran and D-ribose were used as model compounds before analyzing neomycin and its EDTA-derivative. MD simulations were carried out in AMBER 14 with the GLYCAM06 force field. Preliminary data indicated that experimental and computational data agree well.
Rangel, V., Watson, A., & Kooner, A. S. (2017). Conformational Analysis of Neomycin B and Its Derivative. Poster presented at 31st Annual National Conference on Undergraduate Research at University of Memphis, Memphis, TN.