Errors in peptide synthesis are a source of discrepancies in Aβ42 studies
Matulewska-Sobczuk, K.; Bernfur, K.; Thacker, D.; Wallerstein, J.; Stemme, E.; Dear, A.; Lindblom, N.; Andrzejewska, E.; Sneideriene, G.; Knowles, T. P. J.; Gouras, G.; Olsson, U.; Linse, S.; Ortigosa-Pascual, L.
Show abstract
Amyloid-{beta}42 (A{beta}42) aggregation is highly sensitive to experimental conditions, making reproducibility a persistent challenge in Alzheimers disease research. Among the many variables that influence aggregation, the impact of peptide production remains poorly understood. Direct comparison of recombinant and chemically synthesised A{beta}42 prepared under carefully controlled conditions reveals that, despite following similar aggregation mechanism and forming the same predominant fibril structures, synthetic A{beta}42 aggregates more slowly and exhibits reduced seeding efficiency. Consequently, synthetic A{beta}42 produces fewer oligomeric species and displays lower cellular toxicity. Mass spectrometric analyses identify low-abundance sequence imperfections introduced during peptide synthesis as the origin of these differences. By linking synthesis-derived imperfections to variations in A{beta}42 behaviour, this work reveals a previously underappreciated source of discrepancies in amyloid studies. In addition, we provide a framework for evaluating the impact of sequence impurities on biophysical studies that are sensitive to peptide composition.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The Fluorescent Dye 1,6-Diphenyl-1,3,5-Hexatriene Binds to Amyloid Fibrils Formed by Human Amylin and Provides a New Probe of Amylin Amyloid Kinetics 92%
- A Disease-Associated Mutation Impedes PPIA Through Allosteric Dynamics Modulation 91%
- Engineered chimeras unveil swappable modular features of fatty acid and polyketide synthase acyl carrier proteins 90%
Similar papers in this journal
Similar papers in this journal
- Amyloid-β oligomers are captured by the DNAJB6 chaperone: Direct detection of interactions that can prevent primary nucleation 94%
- Quantitating denaturation by formic acid: Imperfect repeats are essential to the stability of the functional amyloid protein FapC 93%
- Structural details of amyloid beta oligomers in complex with human prion protein as revealed by solid-state MAS NMR spectroscopy 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.