The present disclosure provides modified antibodies which contain an antibody or antibody fragment (AB) modified with a masking moiety (MM). Such modified antibodies can be further coupled to a cleavable moiety (CM), resulting in activatable antibodies (AAs), wherein the CM is capable of being cleaved, reduced, photolyzed, or otherwise modified. AAs can exhibit an activatable conformation such that the AB is more accessible to a target after, for example, removal of the MM by cleavage, reduction, or photolysis of the CM in the presence of an agent capable of cleaving, reducing, or photolyzing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

Methods for proteomic screening on random protein-bead arrays by mass spec is described. Photocleavable mass tags are utilized to code a protein library (bait molecules) displayed on beads randomly arrayed in an array substrate. A library of probes (prey) can be mixed with the protein-bead array to query the array. Because mass spec can detect multiple mass tags, it is possible to rapidly identify all of the interactions resulting from this mixing.

The present invention relates to a novel method for diagnosing high-affinity binders, in particular antibodies or autoantibodies, and the identification, characterization and selection of marker sequences and diagnostic use thereof, in particular in the form of a panel. The invention also relates to a singleplex assay in which the discovered selection of marker sequences is used in the form of a panel and high-affinity binders are detected using a single signal.

Provided herein are methods for identifying a compound that alters fluorescence resonance energy transfer (FRET) of a protein. In one embodiment, the method includes providing a target protein, where the target protein includes two heterologous domains, each domain having chromophores that together act as a FRET pair. In another embodiment, the method includes providing a target protein and a second protein, wherein the target protein includes a first heterologous domain including a chromophore, and the second protein includes a second heterologous domain including a chromophore, where the chromophores together act as a FRET pair. The method further includes contacting a sample including the target protein and optional second protein with a test compound to form a mixture, and measuring a fluorescence emission spectrum of the mixture during exposure to a light source. The fluorescence emission spectrum is decomposed into at least two component spectra, where in one embodiment the component spectra include a donor chromophore emission and an acceptor chromophore emission. A ratio (R) is then calculated, and in one embodiment, R is determined according to

[00001]$R=\frac{\mathrm{Acceptor}.Math..Math.\mathrm{emission}}{\mathrm{Donor}.Math..Math.\mathrm{emission}}=\frac{{\mathrm{bF}}_A}{{\mathrm{aF}}_D}.$

Agents and compounds which can be used to modulate the activity of the complement system, novel biological targets associated with such modulation, and pharmaceutical compositions, medicaments and methods of treatment for use in preventing, ameliorating or treating diseases that are characterised by inappropriate complement activity. These diseases include age-related macular degeneration (AMD), meningitis, renal disease, autoimmune disease and inflammation. Therapeutic antibodies and screening assays for identifying agents useful in treating these diseases are also provided.

A new, stable trimeric TNF? structure is disclosed with distorted symmetry which can bind to the TNFR1 receptor to attenuate signalling therefrom, which can be used in the treatment and/or prevention of diseases associated with the soluble TNF?/TNFR1 interaction. Membrane-bound TNF? is not affected in its ability to signal through TNFR2, and thus the new structure of TNF? may be used in therapies which do not significantly raise the risk of infection or malignancy.

Miniature protein scaffolds and compositions thereof (e.g., vaccine formulations) and methods of using same are described herein. In a particular embodiment, the miniature protein scaffold comprises an isolated -strand connected via a loop to a left-handed poly proline type-II (PPII) helix formed in the absence of proline residues.

The present invention provides novel methods and assays for high-throughput screening of combinatorial libraries to identify FPR1 and/or FPR2 ligands (e.g., agonists and/or antagonists), preferably FPR1 agonists and/or FPR2 antagonists, by positional scanning deconvolution. The invention also provides novel FPR1 and FPR2 ligands (e.g, agonists and antagonists), related pharmaceutical compositions and methods of treating FPR1 and FPR2-related disorders.

Water-soluble triazabutadiene molecules and methods for producing and using such compounds. The triazabutadiene molecules may be more labile at pH levels below physiological pH, such as pH 7, pH 6, pH 5, etc. The triazabutadiene molecules and compounds may be used for depositing diazonium salt and/or cargo in a pH-sensitive manner. The triazabutadiene molecules may alternatively be cleaved in reducing conditions or as a light-catalyzed reaction. The compounds herein may be used for delivery of drugs, as part of detection systems, or for other applications such as underwater adhesive applications.

Methods and systems for high-throughput identification of receptor:ligand interactions are provided.