The invention comprises systems, methods and arrays for identification and optimization of novel peptide binders to protein targets. Embodiments include steps of peptide binder discovery, core peptide maturation, N-terminal and C-terminal extension and kinetics analysis of the final peptide binder.

Crosslinking molecules that permit efficient identification of specifically associated proteins and the sites of crosslinking in biological or other samples include two cleavable bonds that are cleavable under the same conditions as peptide bonds in mass spectrometric determinations. Sets of the invention crosslinkers may be provided with isobaric labels containing reporter ions of differing molecular weights to permit relative quantitation of crosslinked protein pairs.

An object of the present invention is to provide a peptide excellent in resistance against metabolism, having a stable structure in vivo, and capable of penetrating a cell membrane and reaching in cells. The present invention provides a macrocyclic peptide having a macrocyclic structure comprised of four or more amino acids. At least two amino acids not adjacent to each other have a hydrophobic side chain and the hydrophobic side chains interact with each other inside the ring of the macrocyclic peptide in a hydrophilic environment.

Provided herein are high-throughput, population-wide serotyping and antibody profiling assays. Disclosed variants of a Digital Serotyping assay employ next generation sequencing to measure the serotyping profile of barcoded subject serum antibodies tested against a range of DNA-tagged pathogen-derived antigens. The disclosed assay setup enables multiplexing in both the sample and antigen dimensions, generating a large multi-dimensional serotyping data set for more comprehensive serotyping profiling of large populations across a large number of antigens and possible pathogens. Moreover, the ability to easily scale and multiplex the number of peptide epitopes allows rapid updating of the assay content to monitor the ever-changing spectrum of pathogens. Additional applications of this technology include cancer immunology and autoimmune conditions (e.g., neoantigen or autoimmune profiling), screening for toxins, antibody therapeutics development, biosecurity, and veterinary medicine.

A method, including (a) providing an array of extant glycans or glycoconjugates, wherein the array comprises a plurality of addresses, wherein different extant glycans or glycoconjugates are attached to different addresses of the array; (b) contacting the array with a plurality of different probes, the different probes recognizing different carbohydrate moieties; (c) detecting positive recognition outcomes of the plurality of different probes at individual addresses of the array, thereby producing outcome profiles for the addresses; (d) providing a database comprising a set of candidate glycans or glycoconjugates, the database comprising, for each candidate glycan or glycoconjugate, the probability of a positive recognition outcome for the plurality of different probes; and (e) determining with a computer, using the database and the outcome profiles, candidate glycans or glycoconjugates in the database corresponding to different extant glycans or glycoconjugates in the array.

The presently disclosed subject matter relates to combinatorial vector cloning and transfection strategies for the generation of targeted integration host cells suitable for the expression of recombinant proteins, as well as targeted integration host cells generated by said strategies and compositions comprising said targeted integration host cells.

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, photolysed, 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 photolysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

The technology described herein is directed to structural analysis, particularly of small proteins via cryo-EM.

The disclosure provides methods and compositions useful for labeling of target molecules with origin-specific nucleic acid identifiers (for example, barcodes), which can be used subsequently to identify, quantify, or otherwise characterize a feature or activity of target molecules originating from a particular discreet volume. Such target molecules can include polypeptides expressed by cells, in which nucleic acid molecules encoding the polypeptides are labeled with the same, or matched, origin-specific nucleic acid identifiers.

The present invention relates, inter alia, to polyspecificity reagents, methods of making the same, and methods of using the same in, inter alia, the selection, screening, enrichment, and identification of non-polyspecific, and thus developable, polypeptides.