The present invention provides a method for making uncapped cysteine protein preparations, including uncapped engineered cysteine antibody preparations. The methods include, inter alia, contacting a reducing agent with engineered cysteine antibody molecules, each of the antibody molecules having at least one capped engineered cysteine residue and at least one interchain disulfide bond and reacting the reducing agent with the antibody molecules under conditions sufficient to uncap engineered cysteine residues and form cap byproducts. The method also includes removing the cap byproduct during the reduction reaction. Substantially all of the interchain disulfide bonds present in the antibody molecules prior to reduction are retained following reduction. Antibody conjugates and methods for preparing antibody conjugates using uncapped antibody preparations are also described.

The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.

Disclosed is a new process and intermediates for preparing dipyrrolidine peptide compounds such as, for example, rapastinel. Advantageously, the process may be industrially scalable and cost-effective and use less toxic reagents and/or solvents. Further, the process may be used to prepare peptide compounds having improved purity.

The present invention provides a method for making uncapped cysteine protein preparations, including uncapped engineered cysteine antibody preparations. The methods include, inter alia, contacting a reducing agent with engineered cysteine antibody molecules, each of the antibody molecules having at least one capped engineered cysteine residue and at least one interchain disulfide bond and reacting the reducing agent with the antibody molecules under conditions sufficient to uncap engineered cysteine residues and form cap byproducts. The method also includes removing the bap byproduct during the reduction reaction. Substantially all of the interchain disulfide bonds present in the antibody molecules prior to reduction are retained following reduction. Antibody conjugates and methods for preparing antibody conjugates using uncapped antibody preparations are also described.

Disclosed is a new process and intermediates for preparing dipyrrolidine peptide compounds such as, for example, rapastinel. Advantageously, the process may be industrially scalable and cost-effective and use less toxic reagents and/or solvents. Further, the process may be used to prepare peptide compounds having improved purity.

The present invention provides a method for making uncapped cysteine protein preparations, including uncapped engineered cysteine antibody preparations. The methods include, inter alia, contacting a reducing agent with engineered cysteine antibody molecules, each of the antibody molecules having at least one capped engineered cysteine residue and at least one interchain disulfide bond and reacting the reducing agent with the antibody molecules under conditions sufficient to uncap engineered cysteine residues and form cap byproducts. The method also includes removing the cap byproduct during the reduction reaction. Substantially all of the interchain disulfide bonds present in the antibody molecules prior to reduction are retained following reduction. Antibody conjugates and methods for preparing antibody conjugates using uncapped antibody preparations are also described.

Disclosed herein are formulations, substrates, and arrays for amino acid and peptide synthesis on microarrays. In certain embodiments, methods for manufacturing and using the formulations, substrates, and arrays including one-step coupling, e.g., for synthesis of peptides in a C.fwdarw.N orientation are disclosed. In some embodiments, disclosed herein are formulations and methods for high efficiency coupling of biomolecules to a substrate.

A method for synthesizing peptide thioesters and a head-to-tail amide cyclic peptide thereof, which belongs to the technical field of chemical pharmaceuticals and fine chemical preparation. The method comprises the following steps: (1) using resin A as a carrier and using a solid-phase synthesis strategy to obtain a resin peptide; (2) cutting the resin to obtain a fully protected peptide; (3) performing an esterification reaction with p-chlorophenyl thiophenol in a TCFH/alkali condensation system to generate p-chlorophenyl thioester; (4) removing the protecting group to obtain a peptide thioester; and (5) further cyclizing to obtain a head-to-tail cyclic peptide. The preparation of the thioester peptide and the head-to-tail amide cyclic peptide provides a simple technical route with wide universality and a high yield, and has a wide range of applications in the technology of chemical pharmaceuticals and fine chemical preparation.

##STR00001##

The present invention provides a means capable of selectively introducing a disulfide bond with respect to two free thiol groups located in a molecule of an organic compound such as a peptide, or the like, in a short time by a simple treatment and also by a chemically stable method.

A nitrogen-containing compound represented by Chemical Formula 1 below or a salt thereof:

##STR00001##

The symbols shown in Chemical Formula 1 are the same as defined in the specification.

Disclosed is a new process and intermediates for preparing dipyrrolidine peptide compounds such as, for example, rapastinel. Advantageously, the process may be industrially scalable and cost-effective and use less toxic reagents and/or solvents. Further, the process may be used to prepare peptide compounds having improved purity.