We will develop new protein-catalyzed capture (PCC) agents for the detection of two important biomarkers of the Plasmodium falciparium strain of malaria in human blood. PCC agents are an emerging class of oligopeptides that can discriminate between targets with only a single amino acid point mutation within living cells. This proposal will leverage their selectivity to develop binders to histidine-rich protein 2 and lactate dehydrogenase. We will develop PCC agents for multiple epitopes on each protein to account for inherent regional diversity within malaria endemic countries and validate their selectivity in human blood. Lead candidates from these screens will be subjected to full molecular characterization to gain an accurate picture of the thermodynamics and kinetics behind their selectivity and sensitivity. Finally, these leads will be incorporated into lateral flow assays wit an eye towards implementation in low-resource areas. The success of our devices will be evaluated on their ability to reliably detect biomarkers in human blood and will serve as a proof of concept for the development of assays for other disease targets based on these materials.
Rapid identification of proteins in the bloodstream enables disease diagnosis without expensive facilities or trained technicians. We will develop new reagents to detect important proteins released by Plasmodium falciparum, the most deadly strain of malaria that infects humans, and incorporate them into paper-based blood tests. The results of this work will inform the development of detection agents relevant to other diseases and establish design principles for these devices for general implementation.
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| Das, Samir; Nag, Arundhati; Liang, JingXin et al. (2015) A General Synthetic Approach for Designing Epitope Targeted Macrocyclic Peptide Ligands. Angew Chem Int Ed Engl 54:13219-24 |
