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Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation
Published on: January 26, 2016
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Cyclic di-peptide in situ inhibited protein-aggregation
Nibedita Ghosh1, Lal Mohan Kundu2
1Centre for the Environment, IIT Guwahati, Assam 781039, India; Symbol Discovery Ltd, Hyderabad 500046, India.
Bioorganic & Medicinal Chemistry Letters
|June 18, 2023
Summary
This study introduces rationally designed peptide inhibitors to prevent protein misfolding and aggregation, a key factor in neurodegenerative diseases like Alzheimer's. These inhibitors show promise in blocking the pathological processes underlying these conditions.
Area of Science:
- Neuroscience
- Biochemistry
- Drug Discovery
Background:
- Protein misfolding and aggregation into β-sheet structures are implicated in various neurodegenerative diseases.
- Diseases such as Alzheimer's, Huntington's, and prion encephalopathies involve the accumulation of specific misfolded protein aggregates.
Purpose of the Study:
- To develop rationally designed peptide inhibitors targeting the aggregation of amyloid-β (Aβ) peptides.
- To investigate a therapeutic strategy focused on inhibiting protein aggregation using peptide inhibitors with recognition and β-breaking components.
Main Methods:
- Utilized the core amyloid-β sequence as the model aggregating peptide (AP).
- Employed the "O → N acyl migration" concept for in situ cyclic peptide formation, creating a bent disruption moiety.
- Characterized aggregation kinetics using biophysical techniques including Thioflavin T assay (ThT), transmission electron microscopy (TEM), circular dichroism (CD), and Fourier-transform infrared spectroscopy (FTIR).
Main Results:
- Designed inhibitor peptides (IP) demonstrated potential in disrupting the aggregation process.
- The biophysical characterization provided insights into the kinetics and mechanisms of aggregation inhibition.
Conclusions:
- The developed inhibitor peptides show promise as a therapeutic strategy against protein aggregation in neurodegenerative diseases.
- This approach offers a potential method to inhibit the pathological accumulation of misfolded proteins.
Keywords:
Acyl migrationAggregated peptidesAmyloidCyclic di-peptideInhibitor peptidesPeptide cyclizationProtein aggregationMore Related Videos
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