Letter: beta-Cyclodextrin affects the formation of isomerization products during peptide deamidation

摘要

Cyclodextrins (CDs) are a group of nontoxic oligosaccharides that are widely used as drug excipients and protein stabilizers. CDs have also been found to reduce the neurotoxicity and fibrillation of amyloid beta (A beta), the major component of the amyloid plaques found in the brain of patients suffering from Alzheimer's disease. The formation of these plaques was found to be enhanced by the presence of iso-aspartic acid (isoAsp) residues in the A beta peptide, which can be formed by deamidation from asparagine (Asa To explore further the influence of CDs on A beta, we investigated three Asn-containing peptides, including A beta 25-35, by electrospray ionization, electron capture dissociation, and Fourier-transform ion cyclotron resonance mass spectrometry to explore details of the deamidation process in the presence and absence of peptide/CD adducts. The results showed that CDs reduced the formation of the isomerization product isoAsp during peptide deamidation. This finding might help to better understand the role of CDs during the protein-aggregation process.