Date of Thesis

Spring 2025

Description

Antibiotic resistance is a growing crisis worldwide, and antimicrobial peptides (AMPs) are emerging as a promising alternative to traditional antibiotics. AMPs, short chains of 10-60 amino acids, are produced by a wide variety of organisms, including insects. This work is focused on the cecropin family, a group of insect AMPs known for their α-helical structure and low toxicity to mammalian cells. Cecropin sequences were sourced from protein databases, with mature peptide forms isolated by removing signal sequences and duplicates. We examine how small variations in amino acid sequences, particularly in regions predicted to serve as hinges between two α-helices, impact both the biophysical properties and antimicrobial behavior of these peptides. The peptides were first categorized by biochemical properties, including hydrophobicity, amphiphilicity, and net charge, to predict their antimicrobial activity. Structural modeling for one category of peptides predicted three primary α-helical conformations, linear, bent, and hinged, suggesting that similarly sequenced peptides can have differing abilities to form multiple conformations and potential membrane insertion mechanisms or capabilities. However, differences in amino acid properties at positions 22 and 23 were suggestive of their predicted structure. Selected peptides were synthesized and their structure was analyzed, which confirmed that they adopt α-helical structures in membrane-mimetic environments, though observed differences in α-helicity between peptides were not correlated with predicted structures. Then, the antimicrobial activity of each peptide was determined against bacterial species including Escherichia coli, Pseudomonas aeruginosa, and two strains of Providencia burhodogranariea. Differences in antibacterial activity were observed, revealing that even small sequence and structural differences can significantly impact peptide efficacy. While increased predicted linearity generally corresponded with greater activity, supporting expectations based on hinge flexibility, this trend was not consistent across all bacterial species. This work aims to improve the rational design of AMPs with improved specificity and potency, addressing the urgent need for new antimicrobial agents in the face of rising antibiotic resistance.

Keywords

cecropin, peptide, antimicrobial, structure, bacteria, insect

Access Type

Honors Thesis (Bucknell Access Only)

Degree Type

Bachelor of Science

Major

Cell Biology/Biochemistry

Minor, Emphasis, or Concentration

Computer Science

First Advisor

Sarah Smith

Second Advisor

Moria Chambers

Third Advisor

Sanjay Dharmavaram

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Available for download on Saturday, May 13, 2028

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