Characterization of Protein Drug Targets and Application of Protein Therapeutics in Parasitic Protozoa

Abstract

This proposal examines several novel routes of protein drug design, their therapeutic applications and potential drug targets in several parasitic protozoa. By comparing similar known proteins and assessing potential associations based on previous research, this paper attempts to discern the function of Plasmodium falciparum serine-repeat antigen 5 and metacaspases in Trypanosoma brucei and Leishmania major. Additionally, compound 9, an improved version of inhibitor GSK3494245/ DDD01305143/compound 8 of 20S protease in L. major, is proposed; by suggesting the development of a more selective inhibitor, increased affinity to specific subunits of 20S protease will improve its potential as a therapeutic agent. Lastly, a novel “conoid cap” therapy is outlined—a protein complex that inhibits mechanical organelles used in penetration of host cells—by assessing the chemical properties such as its resistance to secretory enzymes and identifying/supporting potential binding partners for the cap. Although many of these parasites are neglected by research in the United States, they are still relevant because of their world-wide prevalence and severe effects. This proposal provides a novel perspective on protozoan therapies by investigating modern strategies—such as the use of noncanonical amino acids and BLASTp data—in immunology and new technology in protein characterization.