Date of Graduation
Summer 8-30-2022
Document Type
Thesis
Degree Name
Master of Science in Chemistry
Abstract
Over the past several decades the number of antibiotic resistant bacteria has grown dramatically, in part due to the over-prescription of antibiotics. This rise in antibiotic resistance has led to development of novel antibiotics. An attractive alternative to treat bacterial infections may be the use of antimicrobial peptides due their little-known resistance from bacteria. One such peptide is calcitermin (VAIALKAAHYHTHKE), a 15-residue peptide found in human airways. Calcitermin has antimicrobial properties that target Gram-positive bacteria and is most active in acidic buffer (pH 5.4) due to protonation of its three histidine residues, which allows it to interact with the negatively charged bacterial membrane. Interestingly, it’s activity increases in the presence of Zn(II) and Cu(II), but the mode of action as well as the binding sites remain elusive. These studies also have not described the thermodynamics of metal ion binding which is needed to understand if the interaction has physiological significance. Using isothermal titration calorimetry, the binding thermodynamics of Zn(II) and Cu(II) to calcitermin have been quantified. Zn(II) binds calcitermin with micromolar affinity while Cu(II) binds at nanomolar affinity. These physiologically relevant affinities are entropically driven with modest enthalpic penalties. In addition, the metal ion binding sites were investigated using 1H nuclear magnetic resonance spectroscopy. The metal ions bind to the three histidine residues but also show interactions with many other residues. Taken together, this new insight will lay the foundation for using calcitermin as a potential alternative to traditional antibiotics.
Recommended Citation
Choi, Sohee, "Thermodynamic and Structural Quantification of Metal Ions Binding to the Antimicrobial Peptide Calcitermin" (2022). Master's Theses. 1433.
https://repository.usfca.edu/thes/1433
