DEFINITION
Acylation is the covalent introduction of an acyl group — most often a long-chain fatty acid or fatty-di-acid — onto a peptide side chain, typically at a lysine ε-amino group via an amide bond or through a spacer such as γGlu-2xOEG.
In peptide drug design, acylation is used primarily to introduce reversible albumin binding, dramatically extending plasma half-life. Semaglutide's lysine-26 C18 fatty-di-acid modification is a canonical example.
WHY IT MATTERS
Acylation is the key medicinal-chemistry strategy behind long-acting GLP-1 receptor agonists.
RELATED
Compounds