Computational and Experimental Evaluation of the Stability of a GLP-1-like Peptide in Ethanol-Water Mixtures.

ABSTRACT: Aggregation resulting from the self-association of peptide molecules remains a major challenge during preformulation. Whereas certain organic solvents are known to promote aggregation, ethanol (EtOH) is capable of disrupting interactions between peptide molecules. It is unclear whether it is beneficial or counterproductive to include EtOH in formulations of short peptides. Here, we employed molecular dynamics simulations using the DAFT protocol and MARTINI force field to predict the formation of self-associated dimers and to estimate the stability of a GLP-1-like peptide (G48) in 0-80% aqueous EtOH solutions. Both simulation and experimental data reveal that EtOH leads to a remarkable increase in the conformational stability of the peptide when stored over 15 days at 27 °C. In the absence

SUBMITTER: Lui LH 

PROVIDER: S-EPMC9321252 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature