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 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. 

https://www.pepnet.com/res/uploads/media//GLP-1_versus_Liraglutide_1.jpgTheir work shows how solvent exposure and conditions during synthesis, purification, and formulation can have an impact on oligomer states and fibril formation.1 Read more about the interesting work in the reference below.

Liraglutide
PGL-3781-PI
(M.W. 3751.29) C17H265N43O51     [204656-20-2]
Glucagon-Like-Peptide-1 (GLP-1) Receptor Agonist

Reference:

  1. J.R. Bothe, et al., Mol. Pharmaceutics, (2019).
Industry News , Biologically Active Peptides , Peptides International News , Diabetes

Denise Karounos

See all articles from Denise Karounos

Denise Karounos joined Peptides International in October 2016. After completing her BS in chemistry from West Virginia University, she spent time as an organic chemist at Bachem Bioscience synthesizing peptides and amino acid derivatives. Denise has experience with both solid and solution-phase peptide synthesis, and has worked under both research and cGMP settings. After completing her MBA from Saint Joseph’s University, Denise transitioned into product management of peptides and amino acid derivatives. In her marketing role, she had many duties including but not limited to product management, market research, creating and producing marketing materials, handling US catalog distribution and customer database, email marketing, quoting and inside sales, sales calls, and coordinating and attending trade conferences. 

At PI, Denise's duties encompass both sales and marketing, bringing to bear her extensive lab and sales support experience. Contact her today and see how Denise can assist you with your peptide research project.