Date of Thesis
Spring 2026
Description
Leishmaniasis is a neglected tropical disease caused by the protozoan parasites of the Leishmania genus and spread by the bite of the female sandfly. Due to limited resources and funding, the current treatments for Leishmaniasis are limited, with many of them having life-threatening side effects or requiring extensive resources, such as professional administration, cold storage, and hospitalization, for proper administration. These factors demonstrate a need for new treatment options. One possible approach for treatment is the targeting of vital protein-protein interactions, specifically the homodimerization of ribose-5-phosphate isomerase B (RpiB) of the pentose phosphate pathway. Being able to potentially mimic the necessary protein-protein interactions for dimerization, RpiB binding peptides (RBPs) could interfere with RpiB dimerization and cause parasite death. Ideally, these peptides should be α-helical as this secondary structure has been shown to increase proteolytic stability, cell internalization, and protein-binding affinity, which are necessary traits for therapeutic peptides. An α-helical structure can be induced using a hybrid coordination motif (HCM), where divalent transition metals are used to staple the peptide across two turns of the α-helix, stabilizing the structure. This method of peptide-stapling to induce α-helicity has not yet been validated as an approach to disrupt protein-protein interactions. In this thesis, two metal-binding peptides were designed to inhibit the activity of RpiB. α-helicity was induced in these peptides upon the coordination of Co2+, Cu2+, Ni2+, or Zn2+. This induction of α-helicity was partially dependent on metal-indentity and positively correlated with an increase in proteolytic stability. Additionally, current inhibition data suggests that the metal-bound peptides are capable of inhibiting RpiB activity. This inhibition should be further investigated at more peptide concentrations.
Keywords
Peptides, metal-binding, Leishmaniasis
Access Type
Honors Thesis (Bucknell Access Only)
Degree Type
Bachelor of Science
Major
Cell Biology/Biochemistry
First Advisor
Sarah Smith
Second Advisor
Marie Pizzorno
Recommended Citation
Hauenstein, Greyson, "Designing Metal Binding Alpha-Helical Peptides to Inhibit the Function of Ribose-5-Phosphate Isomerase B in Leishmania Parasites" (2026). Honors Theses. 787.
https://digitalcommons.bucknell.edu/honors_theses/787