Rapid discovery of peptidomimetics as antibody alternatives via epitope-targeted screening

Abstract

We report on the development of peptide-based ligands as antibody alternatives for protein recognition. In the developing world, antibody(Ab)-based rapid diagnostic tests (RDTs) are the preferred method of disease detection for their ease-of-use and low cost relative to techniques such as microscopy and PCR. However, the performance and reliability of RDTs to detect biomarkers are severely hindered by the limitations of Abs. Abs are expensive biomols. that have batch-to-batch variability, exhibit cross-reactivity, and target a single site on a protein. As a result, Abs cannot always sensitively distinguish between disease biomarkers or detect highly polymorphic proteins. Peptide-based ligands are low-cost alternatives to Abs that can be engineered to bind specific protein targets with high affinity. They can be adapted to simultaneously target multiple epitopes, distinguish between homologous structures, and detect proteins with high sequence diversity. We employ a high throughput epitope-targeted screening protocol with combinatorial peptide libraries to rapidly discover ligands for protein recognition. We apply our peptide-based ligands as biosensors towards challenging protein targets for the development of Ab-free RDTs.

Additional details