Aspartate Isomerization Regulates in Situ Assembly of Peptides into Supramolecular Probes for Detection of Protein Carboxyl Methyltransferase in Bladder Cancer.

Abstract

Protein carboxyl methyltransferase (PCMT) restores aspartate isomers in proteins and plays a critical role in cancer prognosis. However, in vivo detection of PCMT remains challenging. Here, we report the aspartate isomerization-regulated in situ assembly of peptides into supramolecular probes within living cells for PCMT detection in bladder cancer. The peptide consists of alternating hydrophobic and hydrophilic residues and contains an isoAsp residue as a kinked site to prevent the facial amphiphilicity of the peptide. Exposure to PCMT converts isoAsp to Asp within the peptide, thereby promoting its assembly into nanofibers. Incorporation of 7-nitro-2,1,3-benzoxadiazole (NBD) into the nanofibers enables PCMT detection based on hydrophobicity-dependent fluorescence of NBD units. Both cellular and animal studies confirm the capability of supramolecular probes for efficient detection of PCMT. Our finding demonstrates an efficient strategy for regulating peptide assembly in living systems and thus provides a new tool for creation of biomedical agents in the future.