Work

Phase-separating peptides identified from complex combinatorial mixtures

Year: 2026
Type: preprint
Abstract: Discovery of peptides that undergo liquid–liquid phase separation (LLPS) is important for establishing sequence–property relationships but systematic approaches have remained elusive so far. Here, we report a tandem mass spectrometry platform to identify peptides prone to LLPS directly from combinatorial peptide libraries encompassing over 44,000 sequences and achieving an 86% true-positive rate across 38 validated candidates. This mixture-based strategy reveals that LLPS forming peptides stabilize aggregation-prone sequences, revealing emergent behavior undetectable in conventional single-peptide analysis. The resulting dataset establishes a foundation for machine learning applications to enable high-throughput prediction of peptide aggregation states.
Source: ChemRxiv
Language: English
Subfield: Spectroscopy
Field: Chemistry
Open Access status: green
OpenAlex ID: W7164585116
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