Title:
NEW RIBOSOMAL TARGETS FOR ANTIBIOTIC DRUG DISCOVERY
Document Type and Number:
WIPO Patent Application WO/2012/142542
Kind Code:
A3
Abstract:
The present invention relates to methods to identify molecules that binds in the neomycin binding pocket of a bacterial ribosome using structures of an intact bacterial ribosome that reveal how the ribosome binds tRNA in two functionally distinct states, determined by x-ray crystallography. One state positions tRNA in the peptidyl-tRNA binding site. The second, a fully rotated state, is stabilized by ribosome recycling factor (RRF) and binds tRNA in a highly bent conformation in a hybrid peptidyl/exit (P/E) site. Additionally, the invention relates to various assays, including single-molecule assay for ribosome recycling, and methods to identify compounds that interfere with ribosomal function by detecting newly identified intermediate FRET states using known and novel FRET pairs on the ribosome. The invention also provides vectors and compositions with an N-terminally tagged S13 protein
Inventors:
BLANCHARD SCOTT C (US)
FELDMAN MICHAEL BRIAN (US)
WANG LEYI (US)
CATE JAMES H DOUDNA (US)
PULK ARTO (US)
ALTMAN ROGER (US)
WASSERMAN MICHAEL R (US)
FELDMAN MICHAEL BRIAN (US)
WANG LEYI (US)
CATE JAMES H DOUDNA (US)
PULK ARTO (US)
ALTMAN ROGER (US)
WASSERMAN MICHAEL R (US)
Application Number:
PCT/US2012/033699
Publication Date:
January 03, 2013
Filing Date:
April 14, 2012
Export Citation:
Assignee:
UNIV CORNELL (US)
UNIV CALIFORNIA (US)
BLANCHARD SCOTT C (US)
FELDMAN MICHAEL BRIAN (US)
WANG LEYI (US)
CATE JAMES H DOUDNA (US)
PULK ARTO (US)
ALTMAN ROGER (US)
WASSERMAN MICHAEL R (US)
UNIV CALIFORNIA (US)
BLANCHARD SCOTT C (US)
FELDMAN MICHAEL BRIAN (US)
WANG LEYI (US)
CATE JAMES H DOUDNA (US)
PULK ARTO (US)
ALTMAN ROGER (US)
WASSERMAN MICHAEL R (US)
International Classes:
G01N23/20; G06F19/16; G01N33/483; G01N33/50
Domestic Patent References:
| WO2008148054A1 | 2008-12-04 |
Foreign References:
| US20020188108A1 | 2002-12-12 |
Other References:
MARIA A. BOROVINSKAYA ET AL.: "Structural basis for aminoglycoside inhibition of bacterial ribosome recycling.", NATURE STRUCTURAL & MOLECULAR BIOLOGY, vol. 14, no. 8, 2007, pages 727 - 732
Attorney, Agent or Firm:
GROLZ, Edward, W. (Scott Murphy & Presser,400 Garden City Plaza,Suite 30, Garden City New York, US)
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