Homocysteine thiolactone (HTL) is an organosulfur compound with the formula . It is the thiolactone (intramolecular thioester) of homocysteine. It is produced by methionyl-tRNA synthetase in an error-editing reaction that prevents translational incorporation of homocysteine into proteins.
HTL can damage proteins through "homocysteinylation" of protein lysine residues.[1] HTL has been reported to form isopeptide bonds with lysine residues in substrate proteins, a post-translational modification known as N-homocysteinylation (N-hcy). This causes protein damage via a thiyl radical mechanism.[2] The drugs citiolone and erdosteine are modified versions of homocysteine thiolactone.
When N-hcy binds α-syn, it exacerbates α-syn aggregation, neurotoxicity, and dopaminergic neuronal degeneration. It also damages the protein DJ-1, contributing to Parkinson's disease.[3]