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.

The present invention discloses a method and apparatus for fully automated iterative polymer synthesis at a large scale.

A synthesis method for low-racemization impurity liraglutide comprises the following steps: performing synthesis to obtain a propeptide, coupling 2 to 5 peptides comprising Thr-Phe on the propeptide by using a solid-phase synthesis method; further, performing solid-phase synthesis to obtain a liraglutide resin; the liraglutide resin is cracked after modification, or the liraglutide resin is directly cracked, purified and frozen dry, so as to obtain the liraglutide. The provided liraglutide synthesis method effectively restrains or reduces the generation of racemization impurity D-Thr.sup.5 highly similar to a product property, which facilitates the purification of the coarse liraglutide, and the high yield of the liraglutide is ensured, thereby greatly reducing production costs; during the synthesis of the liraglutide, the syntheses between dipeptide fragments, tripeptide fragments, the tetrapeptide fragments and pentapeptide fragments and the Gly-resin or the syntheses between the combination of the dipeptide fragments, the tripeptide fragments, the tetrapeptide fragments and pentapeptide fragments and the Gly resin can be carried out at the same time, and accordingly the synthesis time is shortened to some extent.

A synthesis method for low-racemization impurity liraglutide comprises the following steps: performing synthesis to obtain a propeptide, coupling 2 to 5 peptides comprising Thr-Phe on the propeptide by using a solid-phase synthesis method; further, performing solid-phase synthesis to obtain a liraglutide resin; the liraglutide resin is cracked after modification, or the liraglutide resin is directly cracked, purified and frozen dry, so as to obtain the liraglutide. The provided liraglutide synthesis method effectively restrains or reduces the generation of racemization impurity D-Thr.sup.5 highly similar to a product property, which facilitates the purification of the coarse liraglutide, and the high yield of the liraglutide is ensured, thereby greatly reducing production costs; during the synthesis of the liraglutide, the syntheses between dipeptide fragments, tripeptide fragments, the tetrapeptide fragments and pentapeptide fragments and the Gly-resin or the syntheses between the combination of the dipeptide fragments, the tripeptide fragments, the tetrapeptide fragments and pentapeptide fragments and the Gly resin can be carried out at the same time, and accordingly the synthesis time is shortened to some extent.

A peptoid compound, a manufacturing method of a peptoid compound, an oligomer, a pharmaceutical composition, use of the pharmaceutical composition in the preparation of a medicament for detecting or diagnosing a disease related to tyrosine kinase HER2, and a kit for identifying circulating tumor cells are provided, the peptoid compound includes: a cysteine (Cys) subunit, a butanediamine (Nlys) subunit, a 3,4-methylenedioxybenzylamine (Npip) subunit, a 3-aminopropanic acid (Nce) subunit and a 1-naphthylamine (Na) subunit, and both the peptoid compound and the oligomer have a strong ability to bind to HER2 protein on surfaces of circulating tumor cells (CTCs), and a technology of diagnosing breast cancer on the basis of the peptoid compound can realize non-invasive and label-free rapid diagnosis, in addition, the methods for synthesizing the peptoid compound and the oligomer are simple, the preparation efficiency is high, and the production cost is low.

A peptoid compound, a manufacturing method of a peptoid compound, an oligomer, a pharmaceutical composition, use of the pharmaceutical composition in the preparation of a medicament for detecting or diagnosing a disease related to tyrosine kinase HER2, and a kit for identifying circulating tumor cells are provided, the peptoid compound includes: a cysteine (Cys) subunit, a butanediamine (Nlys) subunit, a 3,4-methylenedioxybenzylamine (Npip) subunit, a 3-aminopropanic acid (Nce) subunit and a 1-naphthylamine (Na) subunit, and both the peptoid compound and the oligomer have a strong ability to bind to HER2 protein on surfaces of circulating tumor cells (CTCs), and a technology of diagnosing breast cancer on the basis of the peptoid compound can realize non-invasive and label-free rapid diagnosis, in addition, the methods for synthesizing the peptoid compound and the oligomer are simple, the preparation efficiency is high, and the production cost is low.

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.

Methods and systems for control of solid phase peptide synthesis are generally described. Control of solid phase peptide synthesis involves the use of feedback from one or more reactions and/or processes (e.g., reagent removal) taking place in the solid phase peptide synthesis system. In some embodiments, a detector may detect one or more fluids flowing across a detection zone of a solid phase peptide synthesis system and one or more signals may be generated corresponding to the fluid(s). For instance, an electromagnetic radiation detector positioned downstream of a reactor may detect a fluid exiting the reactor after a deprotection reactor and produce a signal(s). In some embodiments, based at least in part on information derived from the signal(s), a parameter of the system may be modulated prior to and/or during one or more subsequent reactions and/or processes taking place in the solid phase peptide synthesis system. In some embodiments, the methods and systems, described herein, can be used to conduct quality control to determine and correct problems (e.g., aggregation, truncation, deletion) in reactions (e.g., coupling reactions) taking place in the solid phase peptide synthesis system.

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.