Journal
MOLECULES
Volume 28, Issue 22, Pages -Publisher
MDPI
DOI: 10.3390/molecules28227536
Keywords
liraglutide analogue; molecular dynamics simulations; peptide aggregation; peptide nanostructures; therapeutic peptides
Ask authors/readers for more resources
The aggregation properties of LG18, a Liraglutide analogue, were analyzed in this study. Spectroscopic experiments, dynamic light scattering measurements, and molecular dynamics simulations were conducted to investigate the aggregation process of LG18 from sub-micromolar concentrations to micromolar solutions. The critical aggregation concentration of LG18 in water (pH = 8) was found to be 4.3 mu M, and molecular dynamics simulations revealed that LG18 nanostructures are formed by tetramer building blocks.
The pharmacokinetics of peptide drugs are strongly affected by their aggregation properties and the morphology of the nanostructures they form in their native state as well as in their therapeutic formulation. In this contribution, we analyze the aggregation properties of a Liraglutide analogue (LG18), a leading drug against diabetes type 2. LG18 is a lipopeptide characterized by the functionalization of a lysine residue (K26) with an 18C lipid chain. To this end, spectroscopic experiments, dynamic light scattering measurements, and molecular dynamics simulations were carried out, following the evolution of the aggregation process from the small LG18 clusters formed at sub-micromolar concentrations to the mesoscopic aggregates formed by aged micromolar solutions. The critical aggregation concentration of LG18 in water (pH = 8) was found to amount to 4.3 mu M, as assessed by the pyrene fluorescence assay. MD simulations showed that the LG18 nanostructures are formed by tetramer building blocks that, at longer times, self-assemble to form micrometric supramolecular architectures.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available