Disclosed herein are formulations, substrates, and arrays. Also disclosed herein are methods for manufacturing and using the formulations, substrates, and arrays. Also disclosed are methods for identifying peptide sequences useful for diagnosis and treatment of disorders, and methods for using the peptide sequences for diagnosis and treatment of disorders, e.g., celiac disorder. In certain embodiments, substrates and arrays comprise a porous layer for synthesis and attachment of polymers or biomolecules.

The invention provides an amphiphilic coating for the direct and rapid synthesis of an array of peptides and small molecular compounds on a planar surface of a solid support, comprising a hydrophilic chemical structure and a lipophilic group, wherein said peptides and small molecular compounds differ from spot to spot from each other in the chemical structure, characterized in that said amphiphilic coating possesses low wettability to polar aprotic solvents used in the array synthesis; said amphiphilic coating possessing low wettability is designed that it can be converted to a coating possessing high wettability by hydrolysis of the lipophilic group; and said amphiphilic coating comprises an amino group for the reaction with an electrophilic reagent. The invention further provides a solid support comprising said amphiphilic coating and a method for method for the direct and rapid synthesis of an array of peptides and small molecular compounds on a planar surface of a solid support, wherein said planar surface of a solid support comprises said amphiphilic coating. Said method includes the enhancing of the wettability of a glass surface to organic solvents to realize automated on-demand biomolecular array synthesis comprising both, peptides and small molecular compounds. The amphiphilic surface can be switched to a hydrophilic surface, resulting in high density arrays suitable for protein- and cell-based screening.

Methods for the preparation of sample polypeptide fractions are described. Sample polypeptides may be isolated from any of a variety of sources, including biological and non-biological systems. Sample polypeptides may be coupled or conjugated to other molecules to permit characterization of the sample polypeptide fractions. Sample polypeptide fractions may be prepared for analysis by a polypeptide assay.

An elongate solid phase body suitable for performing solid phase synthesis. The solid phase body includes a plurality of enclosures formed of a material of a chemically inert mesh and, within each enclosure, a plurality of solid phase beads.

Systems and methods to characterize dimerization interfaces at the subdomain level of a protein are provided. An exemplary method includes digesting a protein dimer sample into subdomains, labeling the digested protein sample, isolating labeled dimeric and monomeric subdomain fragments, and peptide mapping the labeled sample to determine where the dimer fragments are labeled and where the dimer fragments are not labeled. Regions that show decreased labeling extents in the dimer fraction than that in the monomer fraction are likely involved or in close proximity to the dimerization interface.

Provided herein is a library of antibodies, wherein the library of antibodies can comprise a plurality of monoclonal, monospecific, or immunoprecipitating antibodies. Also provided herein is a method for producing and using the library of antibodies.

Selectively controllable cleavable linkers include electrochemically-cleavable linkers, photolabile linkers, thermolabile linkers, chemically-labile linkers, and enzymatically-cleavable linkers. Selective cleavage of individual linkers may be controlled by changing local conditions. Local conditions may be changed by activating electrodes in proximity to the linkers, exposing the linkers to light, heating the linkers, or applying chemicals. Selective cleaving of enzymatically-cleavable linkers may be controlled by designing the sequences of different sets of the individual linkers to respond to different enzymes. Cleavable linkers may be used to attach polymers to a solid substrate. Selective cleavage of the linkers enables release of specific polymers from the solid substrate. Cleavable linkers may also be used to attach protecting groups to the ends of growing polymers. The protecting groups may be selectively removed by cleavage of the linkers to enable growth of specific polymers.

The invention describes a method of generating antibodies to a mixture of peptidogenic proteins wherein the peptidogenic protein has altered conformational dynamics as compared to a starting protein and wherein the peptidogenic protein has a similar conformation to the starting protein. The peptidogenic proteins can be used to induce an immune response, which can lead to the generation of antibodies and/or can be used to vaccinate a mammal.

Various embodiments generally relate to intelligently designing aptameric peptides for binding with a specific receptor and forming aptameric peptide libraries with the designed peptides. The aptameric peptides libraries can be tissue-specific and be used in drug delivery and therapeutic applications, in which designed peptides can be implanted on exosome surfaces for exosomal cargo delivery to a specific tissue. Various embodiments of the present disclosure involve the use of a generative adversarial network (GAN) machine learning model configured (e.g., trained) and used to output designed peptides that are similar to pre-existing peptides of a peptide dataset but that specifically bind to a selected receptor and have various selected physiochemical properties. In various embodiments, GAN machine learning models may receive representations of the pre-existing peptides and may output representations of designed peptides according to peptide vectorization and encoding schemas based at least in part on the amino acids within a peptide.

The methods described herein provide a means of producing an array of spatially separated proteins. The method relies on covalently attaching each protein of the plurality of proteins to a structured nucleic acid particle (SNAP), and attaching the SNAPs to a solid support.