Cucurbit[7]uril Macrocyclic Sensors for Optical Fingerprinting: Predicting Protein Structural Changes to Identifying Disease-Specific Amyloid Assemblies

• DOI: 10.1021/jacs.2c05969
• Publication Date: 2022-08-01T15:12:54Z
• Authors: Nilanjana Das Saha; Soumen Pradhan; Ranjan Sasmal; Aritra Sarkar; Christian M. Berač; Jonas C. Kölsch; Meenakshi Pahwa; Sushanta Show; Yves Rozenholc; Zeki Topçu; Vivien Alessandrini; Jean Guibourdenche; Vassilis Tsatsaris; Nathalie Gagey-Ei...; Sarit S. Agasti
• Keywords: Biomolecule; Molecular Recognition; Folding (DSP implementation); Amyloid (mycology)

In a three-dimensional (3D) representation, each protein molecule displays specific pattern of chemical and topological features, which are altered during its misfolding aggregation pathway. Generating recognizable fingerprint from such features could provide an enticing approach not only to identify these biomolecules but also gain clues regarding their folding state the occurrence pathologically lethal misfolded aggregates. We report here universal strategy generate fluorescent by employing pan-selective molecular recognition feature cucurbit[7]uril (CB[7]) macrocyclic receptor. implemented direct sensing covalently tethering CB[7] with library reporters. When recognizes geometrical biomolecule, it brings tethered fluorophore into vicinity, concomitantly reporting nature binding microenvironment through change in optical signature. The photophysical properties fluorophores allow multitude probing modes, while structural additional diversity, generating distinct fluorescence biomolecule. first used this rapidly discriminate diverse range analytes. sensor was then applied probe conformational changes structure formation oligomeric fibrillar species proteins. Notably, system allowed us differentiate between different self-assembled forms disease-specific amyloid-β (Aβ) aggregates segregated them other generic amyloid structures 100% identification accuracy. Ultimately, predicted clinically relevant fingerprinting serum samples cohort pregnant women.