# Self‐Assembly of Off‐Target Peptide Sequences: Implications for the Design of Soft Materials

## TL;DR

This paper explores how impurities in peptides can still self-assemble into gels, changing design rules for soft materials.

## Contribution

The study reveals that truncated and epimerized peptides can form gels and alter structures when mixed with parent peptides.

## Key findings

- Truncated and epimerized peptides retain gel-forming ability.
- Mixing peptides with the parent compound creates new self-assembled structures.
- Impurities significantly influence self-assembly outcomes.

## Abstract

The self‐assembly of short peptides into defined nanostructures is one method for preparing soft materials and gels. Indeed, many useful materials can be prepared by the self‐assembly of oligopeptides. The design rules around such peptides are relatively established, and they assume well‐defined and pure materials. In many cases, however, the purity of the peptide is less than 95%, and the ability of likely impurities to self‐assemble is an open question. Here, the self‐assembly of the gel‐forming octapeptide FEFEFKFK and two analogues, EFEFKFK and FEFEfKFK, is discussed to examine the effect of an amino acid deletion and of epimerization at one position. Both the truncated peptide and epimerized peptide can still form gels. Mixing these peptides with the parent FEFEFKFK leads to the formation of new, but different, self‐assembled structures. This has direct implications for the understanding of the necessary design rules for self‐assembly regarding the influence of potential impurity in these systems, as well as demonstrating that much remains to be learned about sequence to structure relationships in self‐assembling peptide systems.

For an ionic complementary peptide, both a truncated peptide and an epimerized peptide can still form gels. Mixing these peptides with the parent FEFEFKFK leads to the formation of new, but different, self‐assembled structures.