Date of Thesis
Spring 2024
Description
Leishmaniasis is a parasitic disease spread by the bite of female sandflies and caused by over twenty species of protozoan parasites. The World Health Organization classifies leishmaniasis as a neglected tropical disease due to its prevalence in impoverished regions and the lack of research on developing better alternatives to current therapies. There is an urgent need to explore more effective treatment strategies since currently available treatments suffer from undesirable side effects due to drug toxicity and emerging drug resistant strains of Leishmania parasites. One possible approach to treating leishmaniasis involves disrupting an essential protein-protein interaction (PPI) in the parasite: the dimerization of ribose-5-phosphate isomerase B (RpiB). In this thesis, RpiB-binding peptides (RBPs) with two amino acid side chains linked via a hybrid coordination motif (HCM) are designed to bind the dimerization interface of RpiB to block formation of functional enzymes and result in parasitic death. RBPs equipped with an HCM coordinate a divalent metal ion of various identities (Co2+, Cu2+, Ni2+, Zn2+) and were hypothesized to induce an α-helical fold in the otherwise unstructured peptide to mimic the native structure of RpiB at the dimerization interface. Induction of α-helicity is advantageous because it is expected to confer properties favorable to a peptide therapeutic such as increased proteolytic stability, improved cellular internalization, and enhanced binding to a protein target. While circular dichroism data suggested that metal-bound RBPs were no more structured than their metal-free counterparts, analysis of the comparative proteolytic stabilities showed that some metal-bound RBPs had greater resistance to proteolytic cleavage.
Keywords
peptide, protein-protein interaction, leishmaniasis, metal binding
Access Type
Honors Thesis (Bucknell Access Only)
Degree Type
Bachelor of Science
Major
Cell Biology/Biochemistry
First Advisor
Sarah Smith
Recommended Citation
Bolorin, Brianna, "Designing Metal-Binding Peptides as Dimerization Disruptors of Ribose-5-Phosphate Isomerase B from Leishmania donovani" (2024). Honors Theses. 675.
https://digitalcommons.bucknell.edu/honors_theses/675