A short peptide synthon for liquid–liquid phase separation

凝聚 化学 原细胞 分区(防火) 合成子 微型反应器 生物分子 二肽 组合化学 分子 相(物质) 纳米技术 色谱法 有机化学 生物化学 催化作用 材料科学
作者
Manzar Abbas,Wojciech P. Lipiński,Karina K. Nakashima,Wilhelm T. S. Huck,Evan Spruijt
出处
期刊:Nature Chemistry [Nature Portfolio]
卷期号:13 (11): 1046-1054 被引量:213
标识
DOI:10.1038/s41557-021-00788-x
摘要

Liquid–liquid phase separation of disordered proteins has emerged as a ubiquitous route to membraneless compartments in living cells, and similar coacervates may have played a role when the first cells formed. However, existing coacervates are typically made of multiple macromolecular components, and designing short peptide analogues capable of self-coacervation has proven difficult. Here we present a short peptide synthon for phase separation, made of only two dipeptide stickers linked via a flexible, hydrophilic spacer. These small-molecule compounds self-coacervate into micrometre-sized liquid droplets at sub-millimolar concentrations, which retain up to 75 wt% water. The design is general and we derive guidelines for the required sticker hydrophobicity and spacer polarity. To illustrate their potential as protocells, we create a disulfide-linked derivative that undergoes reversible compartmentalization controlled by redox chemistry. The resulting coacervates sequester and melt nucleic acids, and act as microreactors that catalyse two different anabolic reactions yielding molecules of increasing complexity. This provides a stepping stone for new coacervate-based protocells made of single peptide species. Liquid–liquid phase separation plays an important role in creating cellular compartments and protocells, but designing small-molecule models remains difficult. A peptide-based synthon for liquid–liquid phase separation consisting of two stickers and a flexible, polar spacer has now been presented. Condensates formed by these synthons can concentrate biomolecules and catalyse anabolic reactions.
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