Creative Biolabs has over a decade of working experience in antibody design and modification to fit various bio-conjugation strategies, especially for the development of antibody-drug conjugates (ADCs).
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.
Some endogenous or engineered sites for the conjugation of cytotoxic payload drugs to an antibody (Antibodies,2015).
To retain antibody bioactivity, mild, near-physiological conditions are often used for conjugation reactions. Under these conditions, endogenous amino acids such as Lys and Cys are chemically reactive and can be used as conjugation sites. Scientists at Creative Biolabs are experienced in performing Lysine conjugation (amine reaction) as well as Cysteine conjugation (thiol reactions) to create ADCs using these endogenous sites. We are also expertise in exploiting Tyrosine conjugation approaches as another innovated endogens site for ADC development.
One downside in using the endogenous amino acids for ADC development is a heavily dispersed drug-to-antibody ratio (DAR) caused by the non-uniform distribution of the conjugation sites, especially in the case of Lysine-based conjugations. To achieve a narrower DAR, Creative Biolabs has explored and adopted a variety of methodologies in antibody design and engineering to introduce a series of specific and chemically versatile conjugation sites into the antibody sequences:
Alongside the efforts of antibody engineering, we also apply several enzymatic or physical approaches to afford site-specific antibody-drug conjugations by modifying the carbohydrate moiety via galactosidases and galactosyltransferases or photo-crosslinking indole-3-butyric acid containing linkers onto antibody nucleotide binding site.
Engineered/non-engineered antibodies are conjugated to the corresponding drug-linker set designed and prepared in DrugLnk and purified via suitable liquid chromatography techniques. The resulted ADCs are characterized for some basic biochemical parameters such as DAR, stability, conjugation site distribution….
Designing a chemically compatible antibody for the conjugation chemistry is a key step that directly dictates the fate of an ADC project. With expertise and dedication, advanced antibody design platform and services from Creative Biolabs will be your best companion in creating customized ADCs. Please contact us for more information and a detailed quote.
Reference:
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