Abstract:
Polypeptides which bind to the helical transmembrane region of membrane proteins are disclosed, as are methods for the design of polypeptides that bind to the transmembrane region of membrane proteins. Also provided are methods for the use of the disclosed polypeptides in various applications, as well as products made through the practice of the instant methods.
Abstract:
Disclosed are methods of identifying subjects with arteriovascular disease, subjects at risk for developing arteriovascular disease, methods of differentially diagnosing diseases associated with arteriovascular disease from other diseases or withiin sub-classifications of arteriovascular disease, methods of evaluating the risk of arteriovascular events in patients with arteriovascular disease, methods of evaluatinig the effectiveness of treatments in subjects with arteriovascular disease, and methods of selecting therapies for treating arteriovascular disease.
Abstract:
Methods and compositions for detecting molecular interactions are provided. Aspects of the invention include the use of a reduced affinity enzyme complementation reporter system. Also provided are systems and kits for use in practicing embodiments of the methods.
Abstract:
Agents and methods for qualitative and quantitative analysis a protein complex or protein complexes using isotope-labeled symmetrical bifunctional crosslinkers and mass spectrometry are provided. Targeting moieties, cell permeability moieties, or affinity moieties, may be appended to the bifunctional crosslinkers. The isotope-labeled symmetrical bifunctional crosslinkers may be used in a kit or as a library.
Abstract:
The present invention relates to a method for identifying protein ligands capable of modulating a cellular response. The method furthermore enables identification of the protein(s) binding to the identified ligand. The method may in particular be useful in drug screening processes and allows screening for biological activity and for drug targets in a high through-put screening format.
Abstract:
The present invention relates to a method for identifying a metabolic stabilizing compound by: a) contacting a candidate compound with GPR43, and b) determining whether GPR43 functionality is modulated, where a modulation in GPR43 functionality is indicative of the candidate compound being a metabolic stabilizing compound. In addition, the invention relates to a method for identifying a metabolic stabilizing compound, comprising: a) contacting a candidate compound with GPR43, and b) determining whether GPR43 functionality is increased, wherein an increase in GPR43 functionality is indicative of the candidate compound being a metabolic stabilizing compound. Further, the invention relates to a method for identifying a metabolic stabilizing compound, comprising: a) contacting a candidate compound with GPR43, and b) determining whether GPR43 functionality is decreased, wherein a decrease in GPR43 functionality is indicative of the candidate compound being a metabolic stabilizing compound.
Abstract:
For purposes of determining the function of a protein, an automated system captures images of cells, each cell located in a predetermined well. After a given cell is exposed to a protein of interest, the system measures the responses of the cell over time, evaluating a variety of cellular parameters. Analytical software within the system evaluates data generated by these measurements, at single-cell resolution. By comparing with various controls the data thus obtained, the system illuminates the function of a protein with respect to one or more disease models, independent of information regarding the structure, chemistry or underlying genomics of the protein.
Abstract:
The present invention relates to immunological cells that are useful in detecting changes in physiological states, which provide for methods of diagnosing diseases or monitoring the course of patient therapy. Also provided are arrays of antigen presenting cell-specific markers for detecting changes in physiological states, and methods of detecting such changes.
Abstract:
The invention provides a protein labeling and interaction detection system based on engineered fragments of fluorescent and chromophoric proteins that require fused interacting polypeptides to drive the association of the fragments, and further are soluble and stable, and do not change the solubility of polypeptides to which they are fused. In one embodiment, a test protein X is fused to a sixteen amino acid fragment of GFP (ß-strand 10, amino acids 198-214), engineered to not perturb fusion protein solubility. A second test protein Y is fused to a sixteen amino acid fragment of GFP (ß-strand 11, amino acids 215-230), engineered to not perturb fusion protein solubility. When X and Y interact, they bring the GFP strands into proximity, and are detected by complementation with a third GFP fragment consisting of GPF amino acids 1-198 (strands 1-9). When GFP strands 10 and 11 are held together by interaction of protein X and Y, they spontaneous association with GFP strands 1-9, resulting in structural complementation, folding, and concomitant GFP fluorescence.
Abstract:
Polypeptides with desirable biophysical properties such as solubility, stability, high expression, monomericity, binding specificity or non-aggregation, including monomeric human VHs and VLs, are identified using a high throughput method for screening polypeptides, comprising the steps of obtaining a phage display library, allowing infection of a bacterial lawn by the library phage, and identifying phage which form larger than average plaques on the bacterial lawn. Sequences of monomeric human VHs and VLs are identified, which may be useful for immunotherapy or as diagnostic agents. Multimer complexes of human VHs and VLs are also identified. The VHs and VLs identified may be used to create further libraries for identifying additional polypeptides. Further, the VHs and VLs may be subjected to DNA shuffling to select for improved biophysical properties.