摘要:
A conditional allelic system is provided where recombinant cells express a fusion protein, where the fusion protein comprises at least a functional portion of a target protein and a destabilizing peptide. The destabilizing peptide binds to a small stabilizing molecule that results in the stabilization of the fusion protein in a functional form, while in the absence of the small stabilizing molecule, the protein function is substantially reduced. The system finds use in studying cellular pathways, preparing transgenic animals that can develop in the presence of the small stabilizing molecule and can then be studied in the presence and absence of the fusion protein to determine the functions and/or effects of target protein function in and/or on various environments. Specifically, a mutated peptide from mTOR is employed as the destabilizing peptide and a modified rapamycin is employed as the small stabilizing molecule.
摘要:
Methods and compositions are provided for reducing aggregation of neurodegenerative proteins associated with neurotoxicity or other proteins. The compounds comprise a first domain or targeting element for binding to the target proteins linked to a second domain or recruiting element that binds to an aggregation inhibiting protein, e.g. a prolyl isomerase. By associating the aggregating forming proteins or neuronal cells under conditions where aggregating proteins are produced with the compound and the aggregation inhibiting protein, aggregation is reduced. The subject agents can be used in assays, investigating the etiology of the neuronal diseases and for prophylaxis and therapy.
摘要:
Methods for screening bifunctional molecules of a drug of interest for modulated pharmacokinetic properties are provided. The subject methods include combining in a reaction mixture a metabolizer of the drug of interest, a reporter of activity of the metabolizer; and a bifunctional compound of the drug of interest. Signal from the reporter is then-evaluated to determine whether the bifunctional compound has a modulated pharmacokinetic property as compared to a free drug control. Also provided are kits and devices for practicing the subject methods of the invention.
摘要:
This invention provides multivalent ligands which carry or display at least one recognition element (RE), and preferably a plurality of recognition elements, for binding directly or indirectly to cells or other biological particles or more generally by binding to any biological molecule. Provided are methods for inducing cellular chemotaxis by introducing a multivalent ligand having at least one N-formyl or N-acyl peptide as a signal recognition element. The signal recognition elements are bound to a molecular scaffold that is a ring-opening metathesis polymerization scaffold. In these scaffolds, the number, spacing, relative positioning and relative orientation of signal recognition elements can be controlled.
摘要:
The invention is directed to compositions of mutated binding proteins containing thiol groups for coupling to sensor surfaces, analyte biosensor devices derived there from, and methods of their use as analyte biosensors both in vitro and in vivo.
摘要:
The invention is directed to compositions of mutated binding proteins containing thiol groups for coupling to sensor surfaces, analyte biosensor devices derived there from, and methods of their use as analyte biosensors both in vitro and in vivo.
摘要:
Compounds useful as protease inhibitors are provided, as are methods of use and preparation of such compounds and compositions containing such compounds. In one embodiment, the compounds are useful for inhibiting HIV protease enzymes, and are therefore useful in slowing the proliferation of HIV.
摘要:
The present disclosure is directed to new compounds useful as modulators of Heat Shock Proteins (HSP). In particular, the present disclosure provides new small molecule peptide-derived compounds having HSP modulation activity, especially Hsp70 modulation activity, and methods of preventing or ameliorating beta-amyloid or polyglutamine aggregation, decreasing cell proliferation, or increasing chaperon activity of the HSPs.