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

作者：Julian Link, Albin Lahu, Manfred Wagner, Tanja Weil, David Y W Ng · 发表于：Beilstein Journal of Organic Chemistry · 年份：2026 · DOI：10.3762/bjoc.22.77 · 研究领域：Medicine

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 (C6) consistently promoting aggregation more effectively than the intermediate analogue (C3), whereas peptides containing the rigid C0-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.