BOC Sciences has built a comprehensive, state-of-the-art technology platform that provides customized antibody-drug conjugate (ADC) services using cysteine conjugation. With a rich background in antibody engineering and pharmaceuticals, BOC Sciences can provide a one-stop full service for ADC development.

The most basic immunoglobulin G molecule consists of two light chains and two heavy chains joined by non-covalent binding forces and disulfide bonds. The two heavy chains are joined by a disulfide bond in the hinge region (Hinge Region). The disulfide bonds linking the two heavy chains in the hinge region can be specifically cleaved by reducing agents (such as MEA, dithiothreitol (DTT), and tris (2-carboxyethyl) phosphine (TCEP)) to generate two half-antibody molecules, each containing an antigen binding site. The smaller antigen binding fragment can be digested by pepsin to antibody f (ab') 2, and then reduced to Fab' fragment by the same method. Both two methods expose the sulfhydryl functional group, which can be coupled with the crosslinker through the sulfhydryl reaction probe. Coupling with the -SH functional group of the hinge region allows the coupled protein or other molecule to be remote from the antigen binding site, ensuring that the binding site is not blocked and retains antigen binding activity.

When preparing ADCs from cysteine obtained by reducing the natural interchain disulfide bond in antibodies, the drug loading depends on the degree of disulfide bond reduction. A fully degraded IgG1 antibody typically has eight cysteine residues. When the disulfide bond is partially reduced or ADCs with a drug-to-antibody ratio (DAR) of 4 will generate a series of mixtures with a DAR of 0, 2, 4, 6 and 8, among which the products with a DAR of 2 and 4 are mainly. BOC Sciences’s scientists are also working on developing new ways to direct attachment sites and control DAR.

Advantages of cysteine conjugation

• cysteine conjugation provides a flexible choice for ADCs that produce non-specific, specific sites.
• Traditional cysteine conjugation is easy to perform, without the need to recombine antibodies or alter the cell culture environment to introduce coupling groups.
• This strategy applies to both Fab and full-length IgG.

We offer the following services

• Conjugation based on inter-chain cysteines
• Conjugation based on engineered cysteines

Our advantages:

• Skilled chemistry team
• Fully equipped analytical support
• High quality, low cost products
• Advanced technology and methods
• Personalized service
• Strict quality control