Acidic Amino Acid Induced 5′-Guanosine Monophosphate Fibrillar Nanozyme: A Highly Efficient Metal-Free Intrinsic Peroxidase Mimic

Integrating pristine biomolecules into supramolecular nanoconfinements has emerged as powerful platforms for creating functional supramolecular architectures with potential in biomedical and biocatalytic applications. Here, we report the spontaneous condensation of 5'-guanosine monophosphate (5'-GMP) into highly ordered G-quadruplex fibrillar superstructures mediated by aspartic acid (AA). Spectroscopic and morphological evolution studies reveal that phase-separated condensation, followed by fibrillar aggregation, governs the assembly process. At higher concentrations, GMP-AA condensation yields a homogeneous hydrogel exhibiting strong, intrinsic, metal-free peroxidase-mimicking activity. The fibrillar confinement facilitates enhanced substrate affinity and hydroxyl radical generation, achieving a <i>K</i>_<i>M</i> of 0.3778 mM (10-fold > HRP) and a <i>V</i>_<i>max</i> of 19.4 × 10^-8 M·s^-1 for H₂O₂. Integrating with natural glucose oxidase enables a robust cascade biocatalyst for glucose detection, extendable to ultrasensitive glutathione sensing. These findings highlight biomolecular condensation as a strategy not only for enzyme-mimicking biohybrids but also for unlocking complexities in biological systems.