Introduction to Interchain Disulfide

What is/are Interchain Disulfide?

Interchain Disulfide - LR004 was covalently conjugated with monomethyl auristatin E (MMAE) via a VC linker by antibody interchain disulfide bond reduction. ^[1] ABSTRACT Site-specific antibody-drug conjugates (ADCs) are designed to overcome the heterogeneity observed with first-generation ADCs that use random conjugation to surface-exposed lysine residues or conjugation to interchain disulfide bonds. ^[2] A large number of bacterial toxins consist of active and cell binding protomers linked by an interchain disulfide bridge. ^[3] During evolution, changes in the intrachain disulfide and interchain disulfide bonds and changes in the glycosylation status of CRP may be responsible for different structure-function relationships of CRP in various species. ^[4] However, they could function as potent inhibitors of viral infection by forming a coiled-coil structure covalently stabilized by interchain disulfide bonds. ^[5] Most site-specific conjugation strategies require modification or removal of antibody glycans or interchain disulfide bonds or engineering of an antibody mutant that bears a reactive handle. ^[6] Herein, we reported a 'one-pot' stapling strategy using isobutylene motifs to stabilise the interchain disulfides of antibodies. ^[7] Further study showed that recombinant SjGILT had obvious thiol reductase activity demonstrated by reducing the interchain disulfide bonds of IgG under acidic conditions. ^[8] Therefore, the neoepitopes recognized by regRF may form directly in the hinge when interchain disulfide bonds are reduced or in the region of the CH2 domain as part of the conformational changes caused by the reduction of the interchain disulfide bonds in the hinge. ^[9] The method involves a combination of some or all of these steps: (1) "mono capture" or "dual capture" of ADCs from serum with streptavidin magnetic beads coated with a generic biotinylated anti-human capture reagent, (2) "on-bead" digestion with IdeS and/or PNGase F, and (3) reduction of interchain disulfide bonds to generate ~25 kDa ADC subfragments, which are finally analyzed by LC-HRMS on a TOF mass spectrometer. ^[10] " Here we describe a protocol for the use of next-generation maleimides (NGMs) for the selective modification of the four interchain disulfide bonds present in a typical IgG1 antibody format. ^[11] In some heart pathologies, interchain disulfide crosslinking in the Tpm molecule occurs. ^[12] We found that Trx reduces the interchain disulfide bonds of the mAbs, after which they remain intact but have altered function. ^[13] SG3710 was designed to rebridge two adjacent cysteines, such as those that form the canonical interchain disulfide bond between the light and heavy chain in Fab fragments. ^[14] Its ability to reduce the interchain disulfides of insulin, in the presence of dithiothreitol, provided further evidence to suggest that it was a Trx. ^[15] This is the first report for the chemical synthesis of insulin‐like heterodimeric glycopeptide having three interchain disulfides, and the synthetic strategy shown here might be useful for the synthesis of other glycosylated four‐disulfide insulin‐like peptides. ^[16] Monoclonal antibody interchain disulfide bond reduction was observed in a Chinese Hamster Ovary manufacturing process that used single‐use technologies. ^[17]

Antibody Interchain Disulfide

LR004 was covalently conjugated with monomethyl auristatin E (MMAE) via a VC linker by antibody interchain disulfide bond reduction. ^[1] Monoclonal antibody interchain disulfide bond reduction was observed in a Chinese Hamster Ovary manufacturing process that used single‐use technologies. ^[2]

interchain disulfide bond

LR004 was covalently conjugated with monomethyl auristatin E (MMAE) via a VC linker by antibody interchain disulfide bond reduction. ^[1] ABSTRACT Site-specific antibody-drug conjugates (ADCs) are designed to overcome the heterogeneity observed with first-generation ADCs that use random conjugation to surface-exposed lysine residues or conjugation to interchain disulfide bonds. ^[2] During evolution, changes in the intrachain disulfide and interchain disulfide bonds and changes in the glycosylation status of CRP may be responsible for different structure-function relationships of CRP in various species. ^[3] However, they could function as potent inhibitors of viral infection by forming a coiled-coil structure covalently stabilized by interchain disulfide bonds. ^[4] Most site-specific conjugation strategies require modification or removal of antibody glycans or interchain disulfide bonds or engineering of an antibody mutant that bears a reactive handle. ^[5] Further study showed that recombinant SjGILT had obvious thiol reductase activity demonstrated by reducing the interchain disulfide bonds of IgG under acidic conditions. ^[6] Therefore, the neoepitopes recognized by regRF may form directly in the hinge when interchain disulfide bonds are reduced or in the region of the CH2 domain as part of the conformational changes caused by the reduction of the interchain disulfide bonds in the hinge. ^[7] The method involves a combination of some or all of these steps: (1) "mono capture" or "dual capture" of ADCs from serum with streptavidin magnetic beads coated with a generic biotinylated anti-human capture reagent, (2) "on-bead" digestion with IdeS and/or PNGase F, and (3) reduction of interchain disulfide bonds to generate ~25 kDa ADC subfragments, which are finally analyzed by LC-HRMS on a TOF mass spectrometer. ^[8] " Here we describe a protocol for the use of next-generation maleimides (NGMs) for the selective modification of the four interchain disulfide bonds present in a typical IgG1 antibody format. ^[9] We found that Trx reduces the interchain disulfide bonds of the mAbs, after which they remain intact but have altered function. ^[10] SG3710 was designed to rebridge two adjacent cysteines, such as those that form the canonical interchain disulfide bond between the light and heavy chain in Fab fragments. ^[11] Monoclonal antibody interchain disulfide bond reduction was observed in a Chinese Hamster Ovary manufacturing process that used single‐use technologies. ^[12]