Detailed Explanation
Acylation is the pharmaceutical innovation that transformed peptide drugs from multiple-daily injections to once-weekly treatments. By covalently attaching a fatty acid chain to a specific amino acid residue on a peptide, chemists create a molecule that reversibly binds to serum albumin — the most abundant protein in blood. While bound to albumin, the peptide is shielded from enzymatic degradation and renal filtration, dramatically extending its circulating half-life.
Semaglutide (Ozempic/Wegovy) is the most commercially successful example. It's a GLP-1 analog acylated with a C18 fatty diacid linked via a mini-PEG spacer to Lys26. This modification extends the half-life from ~2 minutes (native GLP-1) to approximately 7 days, enabling once-weekly subcutaneous injection. Liraglutide (Victoza/Saxenda) uses a C16 fatty acid for once-daily dosing.
The technique is sometimes called lipidation. It preserves the peptide's receptor binding activity while solving the fundamental pharmacokinetic problem that limited peptide therapeutics for decades.
Key Facts
- Extends peptide half-life by enabling albumin binding
- Semaglutide: C18 diacid → ~7 day half-life (weekly dosing)
- Liraglutide: C16 fatty acid → ~13 hour half-life (daily dosing)
- Also called lipidation
- Key innovation behind the GLP-1 drug revolution
Part of the PeptideBond.com education network