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A Genetic Code Expansion‐Derived Molecular Beacon for the Detection of Intracellular Amyloid‐β Peptide Generation
Author(s) -
Sappakhaw Khomkrit,
Jantarug Krittapas,
Slavoff Sarah A.,
Israseipan,
Uttamapinant Chayasith
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202010703
Subject(s) - endocytic cycle , genetic code , amyloid precursor protein , peptide , biogenesis , amyloid (mycology) , molecular beacon , microbiology and biotechnology , intracellular , chemistry , computational biology , biology , biochemistry , alzheimer's disease , gene , disease , cell , medicine , endocytosis , pathology , oligonucleotide , inorganic chemistry
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.