title: The effect of osmolytes on protein fibrillation.
abstract: Osmolytes are small molecules that are exploited by cells as a protective system against stress conditions. They favour compact protein states which makes them stabilize globular proteins in vitro and promote folding. Conversely, this preference for compact states promotes aggregation of unstructured proteins. Here we combine a brief review of the effect of osmolytes on protein fibrillation with a report of the effect of osmolytes on the unstructured peptide hormone glucagon. Our results show that osmolytes either accelerate the fibrillation kinetics or leave them unaffected, with the exception of the osmolyte taurine. Furthermore, the osmolytes that affected the shape of the fibrillation time profile led to fibrils with different structure as revealed by CD. The structural changes induced by Pro, Ser and choline-O-sulfate could be due to specific osmolytes binding to the peptides, stabilizing an otherwise labile fibrillation intermediate.
authors.affiliation: iNANO, Center for Insoluble Protein Structures (inSPIN), Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark.
authors.forename: Francesca
authors.initials: F
authors.lastname: Macchi
authors.affiliation: Hochschule Biberach, Pharmaceutical Biotechnology, Hubertus-Liebrecht-Str. 35, D-88400 Biberach, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Eisenkolb
authors.affiliation: Hochschule Biberach, Pharmaceutical Biotechnology, Hubertus-Liebrecht-Str. 35, D-88400 Biberach, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Kiefer
authors.affiliation: iNANO, Center for Insoluble Protein Structures (inSPIN), Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Otzen
mesh_terms: D000596:Amino Acids / Q000494:pharmacology*; D002942:Circular Dichroism; D005934:Glucagon / Q000378:metabolism*; D008744:Methylamines / Q000494:pharmacology*; D009997:Osmotic Pressure; D066329:Protein Aggregates / Q000187:drug effects*; D011487:Protein Conformation; D017510:Protein Folding / Q000187:drug effects*; D013312:Stress, Physiological; D013402:Sugar Alcohols / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D008744:Methylamines; D066329:Protein Aggregates; D013402:Sugar Alcohols; D005934:Glucagon