|Jennifer V. Hines
Biochemistry Research Facility
The focus of our research group is RNA drug discovery. We employ an interdisciplinary approach to developing RNA-targeted medicinal agents that could potentially treat diseases such as AIDS, multidrug resistant bacterial infections, and cancer. RNA plays a critical role in viral replication, bacterial regulation and cancer biogenesis. By targeting key RNA-mediated regulatory processes for these diseases we hope to ultimately develop novel medicinal agents. Through a combination of chemical, molecular, and structural biology studies we are determining the structure-function relationships of medicinally relevant RNA targets and the structure-activity relationships of small molecule ligands that bind the RNA. We utilize a variety of approaches ranging from biophysical (fluorescence, UV, NMR) to bioinformatics, computational and molecular biology techniques. Our goal is to gain an in-depth understanding of the factors that govern molecular recognition of RNA by small molecules and to use this knowledge in the development of novel medicinal agents.
Structure Activity Studies of RNA-Binding Oxazolidinone Derivatives I. Maciagiewicz, S.Zhou, J.V. Hines, S.C. Bergmeier Bioorg Med Chem Letters, 2011, 4524-4527.
Synthesis and stereospecificity of 4,5-disubstituted oxazolidinone ligands binding to T-box riboswitch RNA C. M. Orac, S. Zhou, J.A. Means, D. Boehme, S. C. Bergmeier, J.V. Hines J. Med. Chem., 2011, In Press.
Anisotropy studies of tRNA - T box antiterminator RNA complex in the presence of 1,4-disubstituted 1,2,3-triazoles S. Zhou, G. Acquaah-Harrison, S.C. Bergmeier, J.V. Hines Bioorg. Med. Chem. Letters, 2011, In press
Library of 1,4-Disubstituted 1,2,3-Triazole Analogs of Oxazolidinone RNA-Binding Agents G. Acquaah-Harrison, S. Zhou, J.V. Hines, S.C. Bergmeier J. Comb. Chem. 2010, 12, 491-496.
Structural probing of the T box antiterminator-tRNA complex J.V. Hines, J.Means, A. Muchenditsi, A. Ageyman Biophysical J., 2010, 98, S263a.
Fluorescence probing of T box antiterminator RNA: Insights into riboswitch discernment of the tRNA discriminator base John A. Means, Crystal M. Simson, Shu Zhou, Aaron A. Rachford, Jeffrey J. Rack, J.V. Hines Biochem. Biophys. Res. Commun., 2009, 389, 616-621.
T box transcription antitermination riboswitch: Influence of nucleotide sequence and orientation on tRNA binding by the antiterminator element Hamid Fauzi, Akwasi Agyeman, J. V. Hines BBA-Gene Regulatory Mechanisms 1789 2009, 185-191.
4,5-Disubstituted Oxazolidinones: High affinity molecular effectors of RNA function. R. Anupam, S. C. Bergmeier, N. J. Green, F. J. Grundy, T. M. Henkin, J. A. Means, A. Nayek, J. V. Hines, Bioorg. Med. Chem. Lett., 2008, 18, 3541-3544 (DOI:10.1016/j.bmcl.2008.05.015)
Characterizing riboswitch function: Identification of Mg2+ binding site in T box antiterminator RNA K.D. Jack, J.A. Means, J.V. Hines, Biochem. Biophy. Res. Commun., 2008, 370, 306-310
Identification of neomycin B-binding site in T box antiterminator model RNA R. Anupam, L. Denapoli, A. Muchenditsi, J. V. Hines, Bioorg. Med. Chem., 2008, 16, 4466-4470
T box riboswitch antiterminator affinity modulated by tRNA structural elements J. A. Means, S. Wolf, A. Agyeman, J. S. Burton, C.M. Simson, J. V. Hines, Chem. Biol. Drug Des., 2007, 69, 139-145.
Structure activity studies of oxazolidinone analogs as RNA-binding agents J. Means, S. Katz, A. Nayek, R.Anupam, J. V. Hines, S. C. Bergmeier, Bioorg. Med. Chem. Letters, 2006, 16, 3600-3604.
In Virto Selection to Identify Determinants in tRNA for Bacillus tyrS T Box Antiterminator mRNA Binding. H. Fauzi, K.D.Jack, J.V. Hines, Nucleic Acids Res. 2005, 8, 2595-2602.
Flourescence resonance energy transfer studies of aminoglycoside binding to a T box antiterminator RNA. J.A. Means, J.V. Hines, Bioorg. Med. Chem. Letters 2005, 15, 2169-2172.