Lysine Conjugation | Abzena

Lysine Conjugation

  • Most commonly used non-specific conjugation strategy
  • Approximately 40 reactive lysine residues in an IgG scaffold are available for modification

Non-specific conjugation

Lysine-based conjugation is one of the most widely used non-specific conjugation strategies. The side-chain ε-amino groups of lysine residues are good nucleophiles, meaning that lysine residues exposed at the surface of antibodies, in areas of structural flexibility, have large solvent accessibility and can be used as sites for drug conjugation. There are currently a number of ADC candidates in the clinic that utilise lysine conjugation techniques as well as the FDA-approved ADCs, Mylotarg® and Kadcyla®.

Typically, lysine conjugations involve reacting linker-payload constructs bearing an activated ester, such as N-hydroxysuccinimidyl ester, with the lysine residues of antibodies to form the ADC. Alternatively, the lysine residues of antibodies can be chemically modified to incorporate other chemical functionalities onto the antibody. For example, the antibody lysines can be reacted with a specific bifunctional linker such as SMCC, in order to introduce thiol reactive, maleimide functional groups which can then be reacted with thiol functional payloads or linker-payloads. At Abzena, we have extensive experience of a range of lysine conjugation techniques used for the development of ADCs.

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