Immunoglobulin G lysine and N-terminal amino groups (IgG primary amines)

Immunoglobulin G (IgG) lysine and N-terminal amino groups are the primary amine functional groups found on the surface of IgG antibodies. These groups consist of the epsilon-amino groups of lysine residues (typically 80-100 per molecule) and the alpha-amino groups at the N-termini of the heavy and light chains (https://doi.org/10.1016/j.addr.2015.06.001). In the context of biopharmaceutical development, these amines are the most frequently utilized sites for the chemical conjugation of therapeutic payloads, such as cytotoxic drugs in antibody-drug conjugates (ADCs) or polyethylene glycol (PEG) for half-life extension (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149763/). Conjugation typically involves a nucleophilic attack by the amine on an electrophilic reagent, such as an N-hydroxysuccinimide (NHS) ester (https://pubchem.ncbi.nlm.nih.gov/compound/N-Hydroxysuccinimide). Because of the high abundance and distribution of these residues across the antibody structure, lysine-based conjugation often results in a heterogeneous mixture of drug products with varying drug-to-antibody ratios (DAR) (https://doi.org/10.1021/acs.bioconjchem.5b00219). While not biological targets for disease treatment, they are essential chemical sites for the engineering of complex biologic drugs (https://www.nature.com/articles/nrd.2017.227).

Other names

IgG lysine residuesIgG N-terminal aminesAntibody primary aminesLysine epsilon-amino groups

These groups serve as nucleophilic sites for the covalent attachment of electrophilic drug-linkers (e.g., NHS esters) to form antibody-drug conjugates (ADCs) or modified biologics.