SAN DIEGO, May 31 /PRNewswire/ -- Triad Therapeutics, Inc. today announced the publication of data on SEA-TROSY, a new technique that enables the use of NMR for structural characterization of protein-ligand interactions for proteins as large as or larger than 70 kDa, which is the size range of most drug targets. The Company is using SEA-TROSY to accelerate structure-based design of gene family-focused, small molecule drug libraries.
The publication entitled ``SEA-TROSY (Solvent Exposed Amides with TROSY): A Method to Resolve the Problem of Spectral Overlap in Very Large Proteins'' appeared in the May 16, 2001 issue of Journal of the American Chemical Society (JACS). The study represents a collaborative effort among scientists at Triad and the University of Wisconsin Medical School.
``SEA-TROSY is a new tool of general utility to expand the study of protein surfaces by NMR spectroscopy,'' said Stephen Coutts, Ph.D., President and Chief Operating Officer at Triad. ``Triad is using the method internally to characterize protein regions that are relevant to drug design. By focusing our analysis on small areas of the protein, we are bypassing the need to solve whole protein structures adding speed and efficiency to drug design.''
The JACS publication describes a new NMR technique, SEA-TROSY (Solvent Exposed Amides -- Transverse Relaxation Optimized Spectroscopy), to study amides that comprise solvent exposed loops in binding sites and on surfaces of proteins. Surface amides are magnetized indirectly through selective excitation of the water molecules surrounding the protein. The solvent exposed amide technique can be combined with most NMR experiments.
NMR is central to Triad's drug discovery program based on the concept that binding site studies are crucial in the drug design process. SEA-TROSY is enabling because it detects only surface amides, ignoring amides buried in the interior of the protein that are not likely to be involved in intermolecular interactions. Triad uses a repertoire of proprietary NMR methods to gather structural information on protein-ligand interactions that illustrate how a ligand interacts with a protein target. Structural information obtained using NMR is applied to design gene family-focused, small molecule drug libraries. The application of SEA-TROSY enhances Triad's drug discovery efforts by allowing the structural characterization of proteins as large as or larger than 70 kDa, which is the size range of most drug targets.
SEA-TROSY improves current NMR methods for the structural characterization of protein-protein and protein-ligand interactions with large, multi-domain proteins. NMR-based structural characterization of large proteins is hindered by broadened NMR signals and spectral overlap, both of which decrease resolution. TROSY was developed to address line-broadening limitations. SEA-TROSY extends TROSY by simplifying the NMR spectra, improving both sensitivity and resolution. |
