Screening of aggregation properties of cyclic peptides by protein nanopores

Abstract

Cyclic peptides have been a promising source of natural pharmaceutical macromolecules with their specific binding docks and enhanced binding affinities. However, the aggregation of cyclic peptides poses a significant challenge, compromising their efficacy and permeability to targets. To address the challenges in detecting and characterizing such aggregation, we introduce nanopore sensing as a promising solution that overcomes the limitations of conventional methods by leveraging ionic current blockades for label-free, high-sensitivity real-time detection. This article investigates the aggregation properties of a cyclic peptide library designed through phage display, screening seven cyclic peptides individually and exploring their co-assembling behaviors. Results reveal that cyclic peptide aggregation is not uncommon under biological conditions, while other chemical and physical characterization experiments further elucidate the detailed mechanism. The study explores the interaction and aggregation properties of cyclic peptides, unveiling the co-assembling phenomena and emphasizing the potential of nanopore-based techniques in advancing peptide aggregation detection and drug development.