biostudies-literatureUnknown133(8)Sappakhaw KPolypeptides generated from proteolytic processing of protein precursors, or proteolytic proteoforms, play an important role in diverse biological functions and diseases. However, their often-small size and intricate post-translational biogenesis preclude the use of simple genetic tagging in their cellular studies. Herein, we develop a labeling strategy for this class of proteoforms, based on residue-specific genetic code expansion labeling with a molecular beacon design. We demonstrate the utility of such a design by creating a molecular beacon reporter to detect amyloid-β peptides, known to be involved in the pathogenesis of Alzheimer's disease, as they are produced from amyloid precursor protein (APP) along the endocytic pathway of living cells.Angewandte Chemie (Weinheim an der Bergstrasse, Germany)3980-3985https://www.ebi.ac.uk/biostudies/studies/S-EPMC10946459biostudies-literatureA Genetic Code Expansion-Derived Molecular Beacon for the Detection of Intracellular Amyloid-β Peptide Generation.PMC10946459Slavoff SASappakhaw KJantarug KUttamapinant CIsrasena NfalseA Genetic Code Expansion-Derived Molecular Beacon for the Detection of Intracellular Amyloid-β Peptide Generation.Polypeptides generated from proteolytic processing of protein precursors, or proteolytic proteoforms, play an important role in diverse biological functions and diseases. However, their often-small size and intricate post-translational biogenesis preclude the use of simple genetic tagging in their cellular studies. Herein, we develop a labeling strategy for this class of proteoforms, based on residue-specific genetic code expansion labeling with a molecular beacon design. We demonstrate the utility of such a design by creating a molecular beacon reporter to detect amyloid-β peptides, known to be involved in the pathogenesis of Alzheimer's disease, as they are produced from amyloid precursor protein (APP) along the endocytic pathway of living cells.2021-01-01T00:00:00Z2021 Feb2025-04-26T12:06:51.742Z2025-02-19T03:08:57.829ZS-EPMC109464593850466710.1002/ange.202010703