Albumin Binding
A drug design strategy where a peptide is modified to reversibly bind to human serum albumin, the most abundant protein in blood plasma. Albumin binding extends a peptide's half-life by reducing renal filtration and protecting against enzymatic degradation. This approach is used in semaglutide and somapacitan.
Technical Context
Albumin has multiple drug-binding sites (Sudlow sites I and II) that accommodate diverse ligands through hydrophobic and electrostatic interactions. Fatty acid-modified peptides bind primarily to albumin's fatty acid binding sites. The binding is reversible — a dynamic equilibrium exists between bound (protected) and free (active) peptide. Only the free peptide can bind to its therapeutic receptor, creating a sustained-release depot effect. The fraction of drug bound to albumin at therapeutic concentrations (typically >99% for lipidated peptides) determines the effective free drug concentration and influences both efficacy and clearance. This pharmacokinetic property is thoroughly characterised during clinical development.