Overcoming synthetic Aβ peptide aging

A new approach to an age-old problem

Claudia Manzoni, Laura Colombo, Massimo Messa, Alfredo Cagnotto, Laura Cant, Elena Del Favero, Mario Salmona

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Investigations of amyloidogenic diseases use synthetic peptides for cell-free and in vitro studies. However, amyloidogenic peptides often show intrinsic variability that markedly affects the reproducibility of experiments. Proof of physicochemical and biological variability with different batches of amyloidogenic peptides have been reported in literature. Here, we show that differences can be observed even within the same batch of Aβ1-42 peptide after storing lyophilised samples at -20°C. This change referred to as 'peptide aging' was reproduced with Aβ1-40 peptide samples by using a series of lyophilisation cycles, showing that lyophilisation, rather than preserving the physicochemical and biological features of Aβ peptides, introduces wide variability. To counteract synthetic peptide aging, we set up a procedure involving the sequential use of trifluoroacetic acid, formic acid and sodium hydroxide solutions that disaggregate preformed seeds and enriched Aβ peptide solutions into monomers and low-molecular-weight oligomers. This procedure enabled us to obtain reproducible physicochemical and biological features of Aβ peptides, irrespective of their age.

Original languageEnglish
Pages (from-to)71-80
Number of pages10
JournalAmyloid
Volume16
Issue number2
DOIs
Publication statusPublished - 2009

Fingerprint

Peptides
formic acid
Freeze Drying
Artificial Cells
Trifluoroacetic Acid
Sodium Hydroxide
Seeds
Molecular Weight

Keywords

  • Aβ peptides
  • Amyloid
  • Lyophilisation
  • Peptide aging reversal
  • Trifluoroacetic acid

ASJC Scopus subject areas

  • Internal Medicine
  • Medicine(all)

Cite this

Overcoming synthetic Aβ peptide aging : A new approach to an age-old problem. / Manzoni, Claudia; Colombo, Laura; Messa, Massimo; Cagnotto, Alfredo; Cant, Laura; Del Favero, Elena; Salmona, Mario.

In: Amyloid, Vol. 16, No. 2, 2009, p. 71-80.

Research output: Contribution to journalArticle

Manzoni, Claudia ; Colombo, Laura ; Messa, Massimo ; Cagnotto, Alfredo ; Cant, Laura ; Del Favero, Elena ; Salmona, Mario. / Overcoming synthetic Aβ peptide aging : A new approach to an age-old problem. In: Amyloid. 2009 ; Vol. 16, No. 2. pp. 71-80.
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