A variety of methodologies in ADC antibody design and engineering introduce a series of specific and chemically versatile conjugation sites into the antibody sequences, including incorporating Cysteine residues into defined sites on an antibody to create thiol-engineered antibody (EnCys-mAb) and conjugate payload drugs onto those Cysteine residues via thiol-based chemistry. https://www.creative-biolabs.com/adc/antibody-design-and-conjugation.htm

1. Antibody Design and Conjugation
Reference: https://www.creative-biolabs.com/adc/antibody-design-and-conjugation.htm

2. content
01 Intoduction of Antibody-drug conjugates
02 Methodologies in antibody design and engineering

3. Intoduction of Antibody-drug conjugates
01

4. Antibody-drug conjugates
Introduction
As one major component of an antibody-drug conjugate (ADC), the antibody is the key for target
specificity and serves as the cargo to deliver the cytotoxic drug (payload). A payload drug can be
attached to different sites on an antibody using diverse conjugation chemistry. Multiple endogenous
amino acids can serve as potential conjugation sites. However, to achieve more precisely controlled
site-directed conjugations and subsequently a narrower distribution of drug-to-antibody ratio (DAR),
special moieties with unique conjugation chemistries are engineered into antibody sequences in our
antibody design services.

5. Some endogenous or engineered sites for the conjugation of cytotoxic payload drugs to an antibody
(Antibodies,2015).

6. Methodologies in ADC antibody design and engineering
02

7. Methodologies
02
Unnatural amino acids (UAAs), such as p-
Acetyl Phenylalanine, are integrated into
antibody sequences via amber stop codon-
mediated transcription and their chemically
diverse side chains are excellent sites to
introduce the payload drug for ADC
preparation
03
Some enzymes recognize and modify certain
amino acids on a peptide motif to yield
chemically activated side chains.
01
Incorporate Cysteine residues into defined
sites on an antibody to create thiol-
engineered antibody (EnCys-mAb) and
conjugate payload drugs onto those
Cysteine residues via thiol-based
chemistry
04
Through antibody design, a “cave” is
created on the desired locations on an
antibody to facilitate meditope trapping
and subsequently, achieve site-specific
meditope-based conjugations.
05
The self-splicing inteins and engineer
intein-fusion antibodies, thereby
achieving C-terminal specific antibody
modification and yielding conjugates
with DARs at 1 or 2.

8. Thanks
Reference: https://www.creative-biolabs.com/adc/antibody-design-and-conjugation.htm