Challenges in Peptide Solubilization - Amyloids Case Study.

Peptide science has been a rapidly growing research field because of the enormous potential application of these biocompatible and bioactive molecules. However, many factors limit the widespread use of peptides in medicine, and low solubility is among the most common problems that hamper drug development in the early stages of research. Solubility is a crucial, albeit poorly understood, feature that determines peptide behavior. Several different solubility predictors have been proposed, and many strategies and protocols have been reported to dissolve peptides, but none of them is a one-size-fits-all method for solubilization of even the same peptide. In this review, we look for the reasons behind the difficulties in dissolving peptides, analyze the factors influencing peptide aggregation, conduct a critical analysis of solubilization strategies and protocols available in the literature, and give some tips on how to deal with the so-called difficult sequences. We focus on amyloids, which are particularly difficult to dissolve and handle such as amyloid beta (Aß), insulin, and phenol-soluble modulins (PSMs).

The application of the hierarchical approach for the construction of foldameric peptide self-assembled nanostructures.

In this paper, we show that a hierarchical approach for the construction of nanofibrils based on α,ß-peptide foldamers is a rational method for the design of novel self-assembled nanomaterials based on peptides. Incorporation of a trans-(1S,2S)-2-aminocyclopentanecarboxylic acid residue into the outer positions of the model coiled-coil peptide led to the formation of helical foldamers, which was determined by circular dichroism (CD) and vibrational spectroscopy. The oligomerization state of the obtained peptides in water was established by analytical ultracentrifugation (AUC). The thioflavin T assay and Congo red methods showed that the obtained α,ß-peptides possess a strong tendency to aggregate, leading to the formation of self-assembled nanostructures, which were assessed by microscopic techniques. The location of the ß-amino acid in the heptad repeat of the coiled-coil structure proved to have an influence on the secondary structure of the obtained peptides and on the morphology of the self-assembled nanostructures.