Crystal memory Affects the Properties of Peptide Hydrogels - The Case of the Cyclic Tyr-Tyr dipeptide

In this work a relationship between the crystal form and morphology and rheological properties of peptide-based hydrogels is examined. We show, that under favorable circumstances a correlation between a starting solid material and a self-assembly processes in solution can exist, leading to different properties of a resulting soft matter. This observation, together with an in-depth analysis of the influence of stereochemistry of self-assembled (ll) and (dl) Tyr-Tyr cyclic dipeptides (cYY) on the observed relationship between gelation and crystallization allowed us to gain a deeper understanding of the peptide hydrogelation processes at a molecular level, using liquid state NMR, rheological studies and scanning electron microscopy. In the course of our studies, several crystal forms of (ll)-cYY has been discovered and described in details using single crystal X-ray diffraction, as well as advanced solid state NMR, X-ray diffraction of powders, thermal analysis, FTIR, circular dichroism and crystal structure prediction (CSP) calculations. Subsequently, we found that while (ll)-cYY easily assembles into hydrogels with different properties depending on the starting solid form, (dl)-cYY always precipitated as one crystal form in the tested conditions. Molecular-level justification for this observation is given.

Automated summary

This study examined the relationship between the crystal form and morphology and rheological properties of peptide-based hydrogels. It was found that there is a correlation between the starting solid material and the self-assembly processes in solution, resulting in different properties of the resulting soft matter. The influence of stereochemistry on the gelation and crystallization processes of Tyr-Tyr cyclic dipeptides was analyzed using various techniques, providing a deeper understanding of the peptide hydrogelation processes at a molecular level. Crystal forms of (ll)-cYY were discovered and described in detail, and the molecular-level justification for the observed precipitation behavior of (dl)-cYY was provided.