Work

The role of spacer length and flexibility in peptide self-assembly

Year: 2026

Type: article

Abstract: Spacer length is a key molecular parameter governing the self-assembly of short peptides. Here, we investigate isoleucine-cysteine-alanine (ICA) tripeptides containing carbon spacers of 6, 3, or 0 methylene units linking the peptide backbone to a hydrophobic naphthalene (Nap) π-block. Using complementary spectroscopic and microscopic techniques, we show that spacer length controls the balance between conformational flexibility and directional non-covalent interactions, thereby dictating assembly pathways and material properties. The results establish a correlation between spacer length and assembly propensity, with the longest spacer (C 6 ) consistently promoting aggregation more effectively than the intermediate analogue (C 3 ), whereas peptides containing the rigid C 0 -spacer fail to develop ordered nanostructures. These findings identify spacer length as a powerful design parameter for tuning peptide self-assembly across multiple length scales.

Source: Beilstein Journal of Organic Chemistry

DOI: 10.3762/bjoc.22.77

Authors: Julian Link, Albin Lahu, Manfred Wagner, Tanja Weil, David Y W Ng

Institution: Max Planck Institute for Polymer Research

Language: English

Topic: Supramolecular Self-Assembly in Materials

Subfield: Biomaterials

Field: Materials Science

Domain: Physical Sciences

Open Access status: diamond

Funder: Deutsche Forschungsgemeinschaft

Award: SFB 1551: Polymerkonzepte zum Verstehen zellulärer Funktionen