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SuFEx-Enabled Polypeptide: Creating Diversified Properties with Minimal Preset Conditions.

Ying Liu1,2, Yajie Chen1, Xue-Ao Mei1

  • 1State Key Laboratory of Chemo- and Bio-Sensing, School of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan Province, 410082, China.

Angewandte Chemie (International Ed. in English)
|August 21, 2025
PubMed
Summary

Researchers developed a new method to easily synthesize and functionalize polypeptides using sulfur(VI)-fluoride exchange (SuFEx) chemistry. This breakthrough enables novel biomaterial designs with enhanced properties and potential applications, including antiviral activity.

Keywords:
Antiviral polymerN‐carboxyanhydridePolymer functionalizationPolypeptideSuFEx

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Area of Science:

  • Polymer Chemistry
  • Biomaterials Science
  • Organic Synthesis

Background:

  • Polypeptide synthesis and functionalization present significant challenges, limiting exploration of their properties and applications.
  • Existing methods often require complex pre-functionalization steps or reactive anchors.

Purpose of the Study:

  • To develop a facile and effective method for polypeptide synthesis and functionalization.
  • To incorporate sulfur(VI)-fluoride exchange (SuFEx) moieties into polypeptides for versatile functionalization.
  • To explore the properties of SuFEx-derived linkages in polypeptides for biomaterial applications.

Main Methods:

  • Incorporation of SuFEx moieties into amino acid N-carboxyanhydrides.
  • Ring-opening polymerization to create functionalized polypeptides.
  • Modification of polypeptides with sulfate or amidosulfonate (sulfamate) linkages.
  • Assessment of linkage properties and synergistic effects with functional moieties.

Main Results:

  • Successfully synthesized polypeptides with incorporated SuFEx moieties.
  • Demonstrated facile functionalization of polypeptides using hydroxyl and amino groups without pre-set conditions.
  • Characterized unique properties of SuFEx-derived sulfate and sulfamate linkages.
  • Showcased synergistic effects in a proof-of-concept with saccharide-modified polypeptides exhibiting antiviral activity and biocompatibility.

Conclusions:

  • SuFEx chemistry provides a versatile platform for polypeptide synthesis and functionalization.
  • SuFEx-derived linkages offer unique properties beneficial for novel biomaterial design.
  • Saccharide-modified polypeptides with SuFEx linkages demonstrate promising antiviral activity and biocompatibility.