Richard H. Ebright--Patents

Issued Patents

Ebright, R., Ebright, Y., and Pendergrast, P.S. (1996) CAP-phenanthroline conjugate for DNA cleavage. US Patent 5,556,949.

Seul, M. and Ebright, R. (2003) Color-encoding and in-situ interrogation of matrix-coupled chemical compounds. Australian Patent 756,945.

Ebright, R. and Ebright, Y. (2005) Bis-transition-metal-chelate probes. US Patent 6,919,333.

Seul, M. and Ebright, R. (2006) Color-encoding and in-situ interrogation of matrix-coupled chemical compounds. US Patent 7,083,914.

Ebright, R. and Ebright, Y. (2006) Reagents and procedures for high-specificity labelling. US Patent 7,141,655.

Ebright, R. and Ebright, Y. (2007) Ultra-high-specificity fluorescent labelling. US Patent 7,282,373.

Seul, M. and Ebright, R. (2007) Color-encoding and in-situ interrogation of matrix-coupled chemical compounds. European Patent 1,003,904.

Seul, M. and Ebright, R. (2008) Farbkodierung und in situ abfrage von matrix-gekoppelten chemischen verbindungen. German Patent 69838067.

Ebright, R. and Ebright, Y. (2008) Bis-transition-metal-chelate probes. US Patent 7,371,745.

Ebright, R. and Ebright, Y. (2008) Reagents and procedures for multi-label high-specificity labelling. US Patent 7,381,572.

Severinov, K., Ebright, R, Pavlova, O., and Sineva, E. (2008) Mutational derivatives of peptide antibiotic microcin J25. US Patent 7,442,762.

Seul, M. and Ebright, R. (2009) Color-encoding and in-situ interrogation of matrix-coupled chemical compounds. Japanese Patent 4,302,780.

Ebright, R. (2012) Switch region: target and method for inhibition of bacterial RNA polymerase. US Patent 8,114,583.

Ebright, R. (2012) Target and method for inhibition of bacterial RNA polymerase. US Patent 8,198,021.

Ebright, R. (2012) RNA exit channel: target and method for inhibition of bacterial RNA polymerase. US Patent 8,206,898.

Seul, M. and Ebright, R. (2013) Color-encoding and in-situ interrogation of matrix-coupled chemical compounds. Canadian Patent 2,291,853.

Ebright, R., Mukhopadhyay, J., Severinov, K., and Semenova, E. (2013) Non-MccJ25-related lariat-peptide inhibitors of bacterial RNA polymerase. US Patent 8,354,246.

Ebright, R. and Wang, D. (2013) Bipartite inhibitors of bacterial RNA polymerase. US Patent 8,372,839.

Ebright, R., and Severinov, K. (2013) Nucleic acid sequences for biosynthesis of non-MccJ25-related lariat peptides. US Patent 8,461,314.

Pending Patents

Ebright, R. Arylpropionyl-alpha-pyrone antibacterial agents. PCT/US11/50660 (filed 9/7/2011; pending).

Ebright, R. and Shen, J. Arylpropionyl-triketone antibacterial agents. PCT/US11/50708 (filed 9/7/2011; pending).

Ebright, R. and Ebright, Y. Antibacterial agents: high-potency myxopyronin derivatives. PCT/US11/52015 (filed 9/15/2011; pending).

Ebright, R., Degen, D., and Ebright, K. Bridge-helix cap: target and method for inhibition of bacterial RNA polymerase. PCT/US12/29679 (filed 3/19/12; pending).

Ebright, R. RNA exit channel: target and method for inhibition of bacterial RNA polymerase. US13474255 (filed 5/17/2012; pending).

Ebright, R. Target and method for inhibition of bacterial RNA polymerase. US13482149 (filed 5/29/2012; pending).

Ebright, R., Zhang, Y., Degen, D., and Ebright, Y. Bipartite inhibitors of bacterial RNA polymerase. PCT/US12/43360 (filed 6/20/2012; pending).

Ebright, R. and Shen, J. Antibacterial agents: phloroglucinol derivatives. PCT/US13/20545 (filed 1/7/2013; pending).

Ebright, R. and Wang, D. Bipartite inhibitors of bacterial RNA polymerase. US13738113 (filed 1/10/2013; pending).

Ebright, R. Antibacterial agents: combination of a rifamycin and a switch region inhibitor. PCT/US13/24765 (filed 2/5/2013; pending).

Ebright, R. and Ebright, Y. Antibacterial agents: side-chain-fluorinated myxopyronin derivatives. PCT/US13/33548 (filed 3/22/2013; pending).

Provisional Patents

Ebright, R., Ebright, Y., Shen, J., Bacci, J., Hiebel, A.-C., Solvible, W., Self, C., and Olson, G. Antibacterial agents. US 61661670 (6/19/12).

Ebright, R. Antibacterial agents. US 61703357 (9/20/12).

Ebright, R. Antibacterial agents. US 61703362 (9/20/12).

Ebright, R. Antibacterial agents. US 61703365 (9/20/12).

Ebright, R., Ebright, Y., Feng, Y., and Degen, D. Antibacterial agents. US 61736476 (12/12/12).

Ebright, R., Feng, Y., and Zhang, Y. Antibacterial agents. US 61736479 (12/12/12).

Ebright, R., Ebright, Y., and Mandal. S. Antibacterial agents. US61759943 (02/01/13).

Dr. Richard H. Ebright

Principal Investigator

Recent Publications

Robb, NC, Cordes T, Hwang L C, Gryte K, Duchi D, Craggs TD, Santoso Y, Weiss S, Ebright RH, Kapanidis AN. 2013. The transcription bubble of the RNA polymerase-promoter open complex exhibits conformational heterogeneity and millisecond-scale dynamics: implications for transcription start-site selection.. Journal of molecular biology. 425:875-885. Abstract

Bacterial transcription is initiated after RNA polymerase (RNAP) binds to promoter DNA, melts ~14 base-pairs around the transcription start site, and forms a single-stranded "transcription bubble" within a catalytically active RNAP-DNA open complex (RP(o)). There is significant flexibility in the transcription start site, which causes variable spacing between the promoter elements and the start site; this in turn causes differences in the length and sequence at the 5' end of RNA transcripts, and can be important for gene regulation. The start-site variability also implies the presence of some flexibility in the positioning of the DNA relative to the RNAP active site in RP(o). The flexibility may occur in the positioning of the transcription bubble prior to RNA synthesis and may reflect bubble expansion ("scrunching") or bubble contraction ("unscrunching"). Here, we assess the presence of dynamic flexibility in RP(o) with single-molecule Förster Resonance Energy Transfer. We obtain experimental evidence for dynamic flexibility in RP(o) using different FRET rulers and labelling positions. An analysis of FRET distributions of RP(o) using burst variance analysis reveals conformational fluctuations in RP(o) in the millisecond timescale. Further experiments using subsets of nucleotides and DNA mutations allowed us to reprogram the transcription start sites, in a way that can be described by repositioning of the single-stranded transcription bubble relative to the RNAP active site within RP(o). Our study marks the first experimental observation of conformational dynamics in the transcription bubble of RP(o) and indicates that DNA dynamics within the bubble affect the search for transcription start sites.

Chakraborty, A, Wang D, Ebright YW, Korlann Y, Kortkhonjia E, Kim T, Chowdhury S, Wigneshweraraj S, Irschik H, Jansen R et al.. 2012. Opening and closing of the bacterial RNA polymerase clamp.. Science (New York, N.Y.). 337(6094):591-5. AbstractWebsite

Using single-molecule fluorescence resonance energy transfer, we have defined bacterial RNA polymerase (RNAP) clamp conformation at each step in transcription initiation and elongation. We find that the clamp predominantly is open in free RNAP and early intermediates in transcription initiation but closes upon formation of a catalytically competent transcription initiation complex and remains closed during initial transcription and transcription elongation. We show that four RNAP inhibitors interfere with clamp opening. We propose that clamp opening allows DNA to be loaded into and unwound in the RNAP active-center cleft, that DNA loading and unwinding trigger clamp closure, and that clamp closure accounts for the high stability of initiation complexes and the high stability and processivity of elongation complexes.

Zhang, Y, Feng Y, Chatterjee S, Tuske S, Ho MX, Arnold E, Ebright RH. 2012. Structural Basis of Transcription Initiation.. Science (New York, N.Y.). 338(6110):1076-1080. AbstractWebsite

During transcription initiation, RNA polymerase (RNAP) binds and unwinds promoter DNA to form an RNAP-promoter open complex. We have determined crystal structures at 2.9 and 3.0 Å resolution of functional transcription initiation complexes comprising Thermus thermophilus RNA polymerase, σ(A), and a promoter DNA fragment corresponding to the transcription bubble and downstream dsDNA of the RNAP-promoter open complex. The structures show that σ recognizes the -10 element and discriminator element through interactions that include the unstacking and insertion into pockets of three DNA bases, and that RNAP recognizes the -4/+2 region through interactions that include the unstacking and insertion into a pocket of the +2 base. The structures further show that interactions between σ and template-strand ssDNA preorganize template-strand ssDNA to engage the RNAP active center.

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