Last go around, the PepTalk looked at fibrils and Amyloid ß-Protein
(Aß), this week, we shift over to another compound that can form
fibrils, Liraglutide. While Aß is of interest in Alzheimer’s research,
liraglutide is an important peptide in diabetes research. Liraglutide powder
is a glucagon-like peptide 1 (GLP-1) receptor agonist. An analog, it
differs from native GLP-1 (7-37) by the addition of a γ-Glu-palmitoyl, a
covalently-linked acyl chain, inserted on the first lysine and with the
substitution of an arginine for the second lysine. A team from Merck
recently published new findings on liraglutide’s stability in Molecular
Pharmaceutics.
Previous research has shown that GLP-1 has an inclination to form
fibrils in a pH-dependent fashion. Typical fibril-forming peptides have a
directly proportional relationship between concentration and fibril
kinetics. However, GLP-1 fibril formation is inversely proportional to
concentration at low pH (<7). Liraglutide readily forms oligomers,
which can be mediated through solvent and pH stabilization. Despite
having modifications, it also follows the same structural properties of
GLP-1. While liraglutide adopts two main oligomer states, it maintains
only one in lyophilized powder form, perhaps from memory effects. In
addition, one state has a better potency than the other.
