Ligands with poly-fluorophenyl moieties promote a local structural rearrangement in the Spinach2 and Broccoli aptamers that increases ligand affinities

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2022-03-29
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Anisuzzaman, Sharif
Geraskin, Ivan M.
Ilgu, Muslum
Bendickson, Lee
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Cold Spring Harbor Laboratory Press for the RNA Society
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Kraus, George
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Nilsen-Hamilton, Marit
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Chemistry

The Department of Chemistry seeks to provide students with a foundation in the fundamentals and application of chemical theories and processes of the lab. Thus prepared they me pursue careers as teachers, industry supervisors, or research chemists in a variety of domains (governmental, academic, etc).

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The Department of Chemistry was founded in 1880.

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Ames National Laboratory

Ames National Laboratory is a government-owned, contractor-operated national laboratory of the U.S. Department of Energy (DOE), operated by and located on the campus of Iowa State University in Ames, Iowa.

For more than 70 years, the Ames National Laboratory has successfully partnered with Iowa State University, and is unique among the 17 DOE laboratories in that it is physically located on the campus of a major research university. Many of the scientists and administrators at the Laboratory also hold faculty positions at the University and the Laboratory has access to both undergraduate and graduate student talent.

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Biochemistry, Biophysics and Molecular Biology

The Department of Biochemistry, Biophysics, and Molecular Biology was founded to give students an understanding of life principles through the understanding of chemical and physical principles. Among these principles are frontiers of biotechnology such as metabolic networking, the structure of hormones and proteins, genomics, and the like.

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The Department of Biochemistry and Biophysics was founded in 1959, and was administered by the College of Sciences and Humanities (later, College of Liberal Arts & Sciences). In 1979 it became co-administered by the Department of Agriculture (later, College of Agriculture and Life Sciences). In 1998 its name changed to the Department of Biochemistry, Biophysics, and Molecular Biology.

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1959–present

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  • Department of Biochemistry and Biophysics (1959–1998)

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Abstract
The interaction of nucleic acids with their molecular targets often involves structural reorganization that may traverse a complex folding landscape. With the more recent recognition that many RNAs, both coding and noncoding, may regulate cellular activities by interacting with target molecules, it becomes increasingly important to understand how nucleic acids interact with their targets and how drugs might be developed that can influence critical folding transitions. We have extensively investigated the interaction of the Spinach2 and Broccoli aptamers with a library of small molecule ligands modified by various extensions from the imido nitrogen of DFHBI [(Z)-5-(3,5-difluoro-4-hydroxybenzylidene)-2,3-dimethyl-3,5-dihydro-4H-imidazol-4-one] that reach out from the Spinach2 ligand binding pocket. Studies of the interaction of these compounds with the aptamers revealed that polyfluorophenyl-modified ligands initiate a slow change in aptamer affinity that takes an extended time (half-life of ∼40 min) to achieve. The change in affinity appears to involve an initial disruption of the entrance to the ligand binding pocket followed by a gradual transition to a more defined structure for which the most likely driving force is an interaction of the gateway adenine with a nearby 2′OH group. These results suggest that polyfluorophenyl modifications might increase the ability of small molecule drugs to disrupt local structure and promote RNA remodeling.
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This article is published as Anisuzzaman, Sharif, Ivan M. Geraskin, Muslum Ilgu, Lee Bendickson, George A. Kraus, and Marit Nilsen-Hamilton. "Ligands with polyfluorophenyl moieties promote a local structural rearrangement in the Spinach2 and Broccoli aptamers that increases ligand affinities." RNA 28, no. 6 (2022): 865-877. DOI:10.1261/rna.079005.121. © 2022 Anisuzzaman et al. This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
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