Abstract: Detection of a security threat to a web browser by: Wrapping a suspect JavaScript code with a detection JavaScript code, wherein, when the wrapped suspect JavaScript code is executed in a web browser, the detection JavaScript code indirectly monitors access to a property of a non-writable, non-configurable JavaScript property, to detect an attempt by the suspect JavaScript code to perform a malicious action in the web browser. Executing the wrapped suspect JavaScript code in the web browser, to effect the monitoring and the detection.

Abstract: The present invention is directed to compounds that specifically target DUSP5 and act as antagonists of that enzyme. Such compounds are useful in the treatment of various conditions including, but not limited to vascular anomalies, cancer, and macular degeneration.

Abstract: Methods for rapidly identifying drug candidates that can bind to an enzyme at both a common ligand site and a specificity ligand site, resulting in high affinity binding. The bi-ligand drug candidates are screened from a focused combinatorial library where the specific points of variation on a core structure are optimized. The optimal points of variation are identified by which atoms of a ligand bound to the common ligand site are identified to be proximal to the specificity ligand site. As a result, the atoms proximal to the specificity ligand site can then be used as a point for variation to generate a focused combinatorial library of high affinity drug candidates that can bind to both the common ligand site and the specificity ligand site. Different candidates in the library can then have high affinity for many related enzymes sharing a similar common ligand site.

Abstract: Disclosed herein are dithio compounds that include at least one fluorophore. The compounds additionally may include a different fluorophore or a non-fluorophore. The dithio compounds may be used as reagents for detecting thiol-containing compounds.

Abstract: Disclosed are assays useful for detecting enzyme activity. The assays may utilize thiol-reactive reagents. The assays may include reacting a reacting mixture that contains an ATP analog (e.g., ATP?S or GTP?S) to form an ADP analog (e.g., ATP?S or GTP?S).

Abstract: A method for preferentially observing an exposed position (1c) of a macromolecule. A sample is obtained having a macromolecule (1a) with a first proton (1) and a second molecule (2a) with a second proton (2); then applying a magnetic field (4) to the sample and irradiating the sample with a pulse sequence (5) that preferentially demagnetizes protons of the macromolecule (1,3) relative to the second proton (2); allowing the second proton (2) to exchange (6) with an exposed proton (1) of the macromolecule; and detecting the magnetization from the relatively magnetized second proton (2), which is now bound to the exposed position (1c) of the macromolecule. The invention also provides a method for observing a position in the macromolecule that bind a ligand.

Abstract: The invention provides a method for determining a structure model for a test ligand bound to a macromolecule binding site. Structural constraints for the test ligand are derived from spectroscopic signals arising from interactions between the test ligand and macromolecule. The structure constraints are used as constraints in docking a structure model of the ligand to a structure model of the macromolecule, or as constraints in overlaying a structure model of the test ligand on the known structure for a reference ligand that binds to the macromolecule. The invention further provides a method for determining a structure model for a macromolecule bound to a ligand. Structural constraints derived from spectroscopically observed interactions of the macromolecule and a reference ligand are used to guide molecular modeling or to evaluate the results of a molecular modeling simulation of the macromolecule.

Abstract: The invention provides methods for generating a library of bi-ligands, comprising (a) determining a common ligand to a conserved site in a receptor family; (b) attaching an expansion linker to the common ligand, wherein the expansion linker has sufficient length and orientation to direct a second ligand to a specificity site of a receptor in the receptor family, to form a module; and (c) generating a population of bi-ligands comprising a plurality of identical modules attached to variable second ligands. The invention also provides methods for identifying a bi-target ligand to a receptor by combining a first bi-ligand to a first receptor in a receptor family and a second bi-ligand to a second receptor in the receptor family. The invention additionally provides bi-ligands and bi-target ligands.

Abstract: The present invention provides compositions containing a common ligand linked to a detectable moiety and provides methods for the preparation of such compositions. The present invention also provides methods for screening candidate ligands for binding to a NAD binding receptor, which include contacting a receptor with a candidate ligand and a composition of the invention followed by evaluation of receptor binding. The screening method of the present invention has broad applicability and can be used to screen large numbers of a wide variety of ligands. The present invention further provides methods for detecting the binding activity of a putative receptor, which include combining the putative receptor with a composition of the invention and evaluating the level of detectable moiety. The invention also provides kits useful for detection of receptors having NAD binding activity and for screening of candidate ligands that bind to a NAD binding receptor.

Abstract: Methods for rapidly identifying drug candidates that can bind to an enzyme at both a common ligand site and a specificity ligand site, resulting in high affinity binding. The bi-ligand drug candidates are screened from a focused combinatorial library where the specific points of variation on a core structure are optimized. The optimal points of variation are identified by which atoms of a ligand bound to the common ligand site are identified to be proximal to the specificity ligand site. As a result, the atoms proximal to the specificity ligand site can then be used as a point for variation to generate a focused combinatorial library of high affinity drug candidates that can bind to both the common ligand site and the specificity ligand site. Different candidates in the library can then have high affinity for many related enzymes sharing a similar common ligand site.

Abstract: The present invention provides common ligand mimics that act as common ligands for a receptor family. The present invention also provides bi-ligands containing these common ligand mimics. Bi-ligands of the invention provide enhanced affinity and/or selectivity of ligand binding to a receptor or receptor family through the synergistic action of the common ligand mimic and specificity ligand that compose the bi-ligand. The present invention also provides combinatorial libraries containing the common ligand mimics and bi-ligands of the invention. Further, the present invention provides methods for manufacturing the common ligand mimics and bi-ligands of the invention and methods for assaying the combinatorial libraries of the invention.

Abstract: The invention provides methods for generating a library of bi-ligands, comprising (a) determining a common ligand to a conserved site in a receptor family; (b) attaching an expansion linker to the common ligand, wherein the expansion linker has sufficient length and orientation to direct a second ligand to a specificity site of a receptor in the receptor family, to form a module; and (c) generating a population of bi-ligands comprising a plurality of identical modules attached to variable second ligands. The invention also provides methods for identifying a bi-target ligand to a receptor by combining a first bi-ligand to a first receptor in a receptor family and a second bi-ligand to a second receptor in the receptor family. The invention additionally provides bi-ligands and bi-target ligands.

Abstract: The invention provides methods for generating a library of bi-ligands, comprising (a) determining a common ligand to a conserved site in a receptor family; (b) attaching an expansion linker to the common ligand, wherein the expansion linker has sufficient length and orientation to direct a second ligand to a specificity site of a receptor in the receptor family, to form a module; and (c) generating a population of bi-ligands comprising a plurality of identical modules attached to variable second ligands. The invention also provides methods for identifying a bi-target ligand to a receptor by combining a first bi-ligand to a first receptor in a receptor family and a second bi-ligand to a second receptor in the receptor family. The invention additionally provides bi-ligands and bi-target ligands.