Many peptide hormones last very little time in circulation: the kidneys filter them out and enzymes break them down within minutes. Lipidation tackles that problem at the root. A spacer and a fatty acid or fatty diacid of 16 to 20 carbons are attached to a side chain (usually a lysine).
That fatty tail makes the peptide bind reversibly to albumin, the most abundant plasma protein. While bound, the peptide is too large to be filtered by the kidney and is shielded from enzymes; it is released gradually.
It is the technology behind once-weekly GLP-1 agonists: semaglutide carries an 18-carbon diacid and tirzepatide a 20-carbon one. Cagrilintide, an amylin analogue, uses the same strategy.
The fatty-acid chain makes up a significant part of the molecular weight and makes these molecules “stickier” (they tend to adsorb to surfaces and aggregate). That is why their handling, their HPLC analysis and their reconstitution have their own particularities.
Related terms
Learn it in depth at the Peptide University
- Half-life engineering · Module 2
- Pharmacology of agonists: single, dual and triple · Module 3
- Metabolic and repair (1–5) · Module 14
Related catalogue compounds
Definition for educational and scientific purposes. It is not medical advice or a recommendation for use. NeoPeptidos products are sold labelled for research use only (RUO).