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Related Experiment Video

Updated: Nov 14, 2025

Rapid One-step Enzymatic Synthesis and All-aqueous Purification of Trehalose Analogues
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Trehalose-based neuroprotective autophagy inducers.

Giulia Assoni1, Giulia Frapporti1, Eleonora Colombo2

  • 1Department of Cellular, Computational And Integrative Biology, (CIBIO), Via Sommarive 9, I-38123 Povo, TN, Italy.

Bioorganic & Medicinal Chemistry Letters
|March 11, 2021
PubMed
Summary

Researchers designed trehalose-based compounds to enhance autophagy. Trehalose-bearing gold nanoparticles (AuNPs) effectively induced autophagy at low concentrations without toxicity.

Keywords:
AutophagyChemical probesNanoparticlesNeurodegenerationProdrugsTrehalose

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Area of Science:

  • Biochemistry
  • Nanotechnology
  • Cell Biology

Background:

  • Trehalose is a natural disaccharide with potential therapeutic properties, including autophagy induction.
  • Developing more potent and bioavailable trehalose derivatives is crucial for therapeutic applications.
  • Understanding the molecular mechanisms of trehalose-induced autophagy is an ongoing research area.

Purpose of the Study:

  • To design and synthesize novel trehalose-centered compounds as autophagy inducers.
  • To evaluate the potency and bioavailability of these compounds compared to free trehalose.
  • To investigate the molecular mechanism of action for promising candidates.

Main Methods:

  • Rational design and synthesis of trehalose intermediates, prodrugs, probes, and nanovectors.
  • Evaluation of autophagy-inducing properties of synthesized compounds in vitro.
  • Assessment of compound toxicity at effective concentrations.

Main Results:

  • Small molecule derivatives (compounds 2-11) showed no significant autophagy induction at sub-millimolar concentrations.
  • Trehalose-bearing polyethylene glycol-functionalized gold nanoparticles (PEG-AuNPs 12a) demonstrated measurable autophagy induction.
  • Autophagy induction by PEG-AuNPs 12a was observed at an estimated trehalose concentration of 40 μM.
  • No significant toxicity was observed for PEG-AuNPs 12a at the effective autophagy-inducing concentration.

Conclusions:

  • Trehalose-bearing nanovectors, specifically PEG-AuNPs, represent a promising strategy for enhanced autophagy induction.
  • Nanoparticle formulation significantly improves the efficacy of trehalose as an autophagy inducer.
  • This study provides a foundation for developing nanoparticle-based therapeutics targeting autophagy.