Chinese Association of Idaho State University (CAISU)
Structural Relationships Part II: Liraglutide
Structural Relationships Part II: Liraglutide
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.
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.
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