The amyloid peptide Aβ (1-42), or other amyloid mutants may form insoluble aggregates during storage. Aβ (1-42) is soluble in hexafluoroisopropanol (HFIP), DMSO, 0.1% aqueous ammonia, 50 mM TRIS ∙ HCl, or 1 mM NaOH. Reconstitution in HFIP or DMSO takes time whereas ammonia rapidly dissolves the peptide. The volatile solvent HFIP is usually evaporated leaving a residue of monomeric, soluble Aβ (1-42), which can be reconstituted with the chosen buffer at pH 7.4 to induce fibrillation. Aβ (1-42) solutions in DMSO or aqueous bases can be diluted directly with a working buffer.
Peptide science is expanding rapidly due to the potential applications of these biocompatible and bioactive molecules. However, their use in medicine is limited by several factors, with low solubility being a significant hurdle in early drug development. Solubility is crucial but not well understood, and no universal method exists for peptide solubilization. This review examines the challenges in dissolving peptides and the factors influencing their aggregation and evaluates various solubilization strategies. Here are some practical tips for handling difficult sequences, with a focus on challenging amyloids like amyloid beta (Aβ), insulin, and phenol-soluble modulins (PSMs). Download the reference Here.