Molecular Design of β‐Sheet Peptide for the Multi‐Modal Analysis of Disease

Intermolecular forces constrain peptide conformation. However, the role of each intermolecular force in constraining peptide conformation remains poorly understood. In this work, we show that aromatic-aromatic interactions drive peptides into β-sheets, and the hydrophobic effect determines the assembly speed of peptides. By using intermolecular forces to artificially control the assembly of β-sheets, a multi-modal analytical system was developed that allows five readouts and dual qualitative-quantitative analysis, and satisfies both point-of-care testing (POCT) and laboratory-based testing. For Mycoplasma Pneumoniae diagnosis, this system eradicates misdiagnosis (from 30 % to 0 %) and broadens the linear range by three-fold, both of which are critical for guiding therapy. This work not only illustrates exact roles of intermolecular forces in driving the formation of β-sheets, but also provides a guideline for the construction of a multi-modal analytical system for disease diagnosis.