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Structurally Resilient Peptide Assembly Regulates Pathogenic Galectin-10 Crystallization To Mitigate Crystallopathy

Shanshan Mo1, Lanlan Yu1, Xiaolu Li1

  • 1State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, P. R. China.

Journal of the American Chemical Society
|March 11, 2026
PubMed
Summary
This summary is machine-generated.

A novel peptide, ISQ, effectively dissolves galectin-10 (Gal-10) crystals, reducing airway inflammation and offering a new treatment for crystallopathy. This self-assembling peptide shows promise for conditions driven by pathogenic protein crystallization.

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Area of Science:

  • Biochemistry
  • Immunology
  • Nanotechnology

Background:

  • Pathogenic protein crystallization in vivo causes inflammation and tissue damage, posing a therapeutic challenge.
  • Galectin-10 (Gal-10) crystallization is a key driver of airway inflammation, activating IL-1β pathways and promoting neutrophilic inflammation.

Purpose of the Study:

  • To develop and characterize ISQ, a novel self-assembling peptide targeting Gal-10 crystallization.
  • To evaluate the therapeutic potential of ISQ in preclinical models of Gal-10 crystal-induced airway inflammation.

Main Methods:

  • ISQ was designed to target and dissolve Gal-10 crystals.
  • ISQ's binding affinity and self-assembly properties were assessed in vitro.
  • Therapeutic efficacy was evaluated in a murine model and primary patient-derived airway epithelial cells.

Main Results:

  • ISQ binds Gal-10 with nanomolar affinity (KD = 2.1 nM) and dissolves preformed crystals.
  • ISQ self-assembles into stable nanostructures with high thermal resilience.
  • Intratracheal ISQ administration significantly reduced airway inflammation, cytokine production, and neutrophil infiltration in a murine model.

Conclusions:

  • ISQ is a first-in-class self-assembling peptide therapeutic that disrupts pathogenic protein crystallization.
  • ISQ demonstrates significant therapeutic efficacy in preclinical models of Gal-10 crystallopathy.
  • ISQ offers a promising new treatment strategy for inflammatory conditions driven by protein crystallization.