Miscellaneous lysine-containing proteins

Miscellaneous lysine-containing proteins is a collective term used in pharmacological databases to describe a broad and heterogeneous group of proteins that undergo non-specific covalent modification by certain drugs. The most prominent example is aspirin (acetylsalicylic acid), which, in addition to its primary inhibition of cyclooxygenase enzymes, acts as an acetylating agent that transfers its acetyl group to the epsilon-amino groups of accessible lysine residues on various proteins (DrugBank DB00945; https://go.drugbank.com/targets/448). Common substrates for this non-selective modification include high-abundance proteins such as human serum albumin and hemoglobin, which can lead to alterations in their structural integrity and physiological function (Walker, 1976, "The acetylation of plasma proteins by aspirin"; https://pubmed.ncbi.nlm.nih.gov/1253055/). These interactions are generally classified as off-target effects rather than therapeutic mechanisms. A significant clinical concern regarding these modifications is the formation of drug-protein adducts, which can act as haptens and trigger immune-mediated hypersensitivity reactions (Park et al., 2005, "Drug-protein adducts: mechanisms of formation and biological consequences"; https://pubmed.ncbi.nlm.nih.gov/15901334/). Because this category represents a generalized chemical reactivity across the proteome rather than a specific functional entity, it is not considered a valid therapeutic target for drug discovery.

Other names

Lysine-containing proteinsProtein lysine residuesProtein-bound lysine

Covalent acetylation or modification of the epsilon-amino group of lysine residues