Abstract
Background: Amyloidosis is defined as a generic term given to a series of proteins/ polypeptides in the form of amyloid fibrils that are deposited in the tissues and give rise to a set of clinical disorders.
Objectives: This work developed an approach to first examine chain association propensities of several amyloidogenic peptides: SNNFGAILSS from the islet amyloid polypeptide (coded IAPP), NAGDVAFV from the protein responsible for corneal amyloidosis (coded Lactoferrin), and (1-42) β-amyloid (coded Amyloid).
Methods: Fmoc-synthesis protocol was applied for the synthesis of IAPP and Lactoferrin whereas Amyloid was synthesized through the Boc-chemistry as early detailed.
Results and Conclusion: The fluorescence and light scattering experiments results indicated that Amyloid revealed a surprising reduction in the aggregation process as a function of time (decrease of about 20-30% in 3 days) through both methods. In contrast, the aggregation intensity of IAPP increased around 35% after 3 days via a light scattering procedure. These findings are very relevant for interpretation of the aggregation phenomenon of amyloidogenic peptides.
The final part of this work proposed rules for dissolution of aggregated structures based on the Lewis acid and Lewis base properties of solvents. Very low solubility values (6 to 15%) were measured for peptides in water but with increased to around 90% in strong nucleophilic or strong electrophilic organic solvents. However, care should be taken when strong nucleophilic solvents such as DMSO are mixed with the strong electrophilic such as water. Both solvent molecules tend to attract each other rather than to dissolve peptide chains thus lowering the capacity of this type of solution for fibril dissolution.
Keywords: Aggregation, amyloid fibrils, amyloidosis, fibril formation, peptide aggregation, peptide solubility.
Graphical Abstract
Related Journals
Current Protein & Peptide Science
Related Books
Frontiers in Protein and Peptide Sciences
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