Scholarlink

<p>Designing small-molecule-based (MW ≤ 1500) self-coacervates and tuning their dynamic properties holds great significance in the regulation of biological events. Herein, we designed a series of p<i>K</i><sub>a</sub> tunable polyionic lipidated flavonoids (LFs), where the aromatic core of flavonoid and the acyl chains serve as stickers, the hydrophilic polyanionic moieties interact via multivalent COO‾…HOOC hydrogen bond formation, leading to coacervation at low concentrations (10 µM). Inspired by nature’s selection of amino acids (glutamic acid vs 2-amino hexane dioic acid) with the profound role of methylene units, we screened a library of LFs to explore the influence of methylene linker length (n = 0-3). FRAP studies suggest that shorter linkers (n = 0, 1) produce gel-like coacervates, whereas longer linkers (n = 2, 3) yield more fluidic droplets. The self-coacervates exhibited strong membrane association, resulting in the formation of 2D domains and/or nano-coacervate-like domains within the lipid bilayer. The domains MFEA (n = 2) are membrane-active, inhibit membrane fusion, and protect the cells from SARS-CoV-2 and influenza infections, highlighting the potential as a broad-spectrum antiviral. Our design of amphiphilic self-coacervates offers a versatile new platform for engineering functional materials and highlights the role of methylene linker length for tuning coacervate mechanics.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Structural and functional role of methylene linkers in self-coacervation-mediated membrane interaction and antiviral defense

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月9日

查看全文
  • Nikesh Dewangan,
  • Indrani Das Jana,
  • Priyaraj Pal,
  • Arindam Mondal,
  • Pradip Kumar Tarafdar

摘要

Designing small-molecule-based (MW ≤ 1500) self-coacervates and tuning their dynamic properties holds great significance in the regulation of biological events. Herein, we designed a series of pKa tunable polyionic lipidated flavonoids (LFs), where the aromatic core of flavonoid and the acyl chains serve as stickers, the hydrophilic polyanionic moieties interact via multivalent COO‾…HOOC hydrogen bond formation, leading to coacervation at low concentrations (10 µM). Inspired by nature’s selection of amino acids (glutamic acid vs 2-amino hexane dioic acid) with the profound role of methylene units, we screened a library of LFs to explore the influence of methylene linker length (n = 0-3). FRAP studies suggest that shorter linkers (n = 0, 1) produce gel-like coacervates, whereas longer linkers (n = 2, 3) yield more fluidic droplets. The self-coacervates exhibited strong membrane association, resulting in the formation of 2D domains and/or nano-coacervate-like domains within the lipid bilayer. The domains MFEA (n = 2) are membrane-active, inhibit membrane fusion, and protect the cells from SARS-CoV-2 and influenza infections, highlighting the potential as a broad-spectrum antiviral. Our design of amphiphilic self-coacervates offers a versatile new platform for engineering functional materials and highlights the role of methylene linker length for tuning coacervate mechanics.