Incorporation of Unnatural Amino Acids into antibody Service

Background

Traditional antibody-drug conjugates (ADCs) usually rely on random conjugation of lysine amino groups or cysteine thiol groups on antibodies. Since an antibody molecule contains about 80 to 90 lysine residues, the conjugation reaction may occur at nearly 40 different sites; while the cysteine obtained by reducing the interchain disulfide bond provides more conjugation sites, it will destroy the structural integrity of the antibody. This random conjugation method causes traditional ADCs to be highly heterogeneous mixtures with poor uniformity and low stability, which in turn affects the efficacy and therapeutic window.

In contrast, site-specific conjugation technology can achieve site-specific and quantitative conjugation of antibodies and toxin molecules, giving ADCs a better drug-antibody ratio (DAR), higher uniformity, better stability, and batch-to-batch reproducibility. This technology not only improves the activity and pharmacokinetic properties of ADCs, but is also more suitable for large-scale production.

Unnatural amino acids: a new way to achieve site-specific conjugation

Among natural amino acids, only lysine and cysteine can be used for conjugation, which limits the precise design of ADCs. However, through genetic codon expansion technology, unnatural amino acids (UAA) can be introduced into recombinant antibodies, thereby providing new, specifically conjugated chemical groups. Profacgen provide professional unnatural amino acid (UAA) incorporation into antibody services. Through advanced genetic code expansion technology, customized UAA is precisely inserted into specific antibody sites to achieve:

Application

Precision ADC development

By inserting non-natural amino acids containing reactive groups such as azide/keto groups at specific sites, quantitative coupling of toxin molecules is achieved, significantly improving the uniformity and stability of ADCs, making the drug-antibody ratio (DAR) precisely controllable, reducing toxic side effects, and improving pharmacokinetic properties.

Bispecific antibody optimization

Introducing complementary click chemical groups on two different antibody chains, achieving efficient directional assembly through bioorthogonal reactions, and increasing the correct pairing rate of bispecific antibodies to more than 90%, greatly simplifying the purification problems in traditional development.

Antibody long-term modification

Integrating PEGylation modification sites at specific sites in the Fc region to achieve monodisperse site-specific modification, effectively extending the half-life of antibodies, and completely retaining antigen binding activity, avoiding potency loss caused by random PEGylation.

Service Procedure

Profacgen provides full-process services from design to production to ensure that unnatural amino acids (UAA) are accurately integrated into antibodies to meet the needs of ADC, bispecific antibodies, and long-acting modifications. The following is our standardized service process:

Figure 1. Service Process.

Our Advantages

• Stable and reliable incorporation technology: using a mature orthogonal translation system to achieve efficient UAA site-specific incorporation.
• Rich UAA selection: providing a variety of functional non-natural amino acids to meet different modification needs.
• Complete technical services: providing a full-process solution from vector construction to protein purification.
• Scalable expression system: supporting production needs from laboratory trials to pilot scale.
• Strict quality control standards: ensuring product quality through multiple tests such as mass spectrometry.

FAQs

Please contact us to provide more detailed information for evaluation.