The study introduces a new azobenzene-based amino acid, AMPO, designed to control β-hairpin formation in polyQ polypeptides, which are associated with neurodegenerative diseases such as Huntington's disease (HD). AMPO overcomes the limitations of previous azobenzene-based β-turn mimics by improving photochemical properties and better mimicking the desired β-turn structure. The cis isomer of AMPO effectively stabilizes the β-hairpin conformation, while the trans isomer disrupts it. Using electron microscopy and solid-state NMR (ssNMR), the researchers found that only the cis isomer of AMPO reproduced the spectral fingerprints of toxic, β-hairpin-containing fibrils formed by mutant huntingtin protein fragments in HD. This work provides a tool to better understand the role of β-hairpin structures in protein aggregation processes in HD and other amyloid-related neurodegenerative diseases.The study introduces a new azobenzene-based amino acid, AMPO, designed to control β-hairpin formation in polyQ polypeptides, which are associated with neurodegenerative diseases such as Huntington's disease (HD). AMPO overcomes the limitations of previous azobenzene-based β-turn mimics by improving photochemical properties and better mimicking the desired β-turn structure. The cis isomer of AMPO effectively stabilizes the β-hairpin conformation, while the trans isomer disrupts it. Using electron microscopy and solid-state NMR (ssNMR), the researchers found that only the cis isomer of AMPO reproduced the spectral fingerprints of toxic, β-hairpin-containing fibrils formed by mutant huntingtin protein fragments in HD. This work provides a tool to better understand the role of β-hairpin structures in protein aggregation processes in HD and other amyloid-related neurodegenerative diseases.