Bioactive Peptides as Antibacterial Agents and Visual Transduction

Bioactive peptides (BPs) are specific protein fragments which positively impact bodily functions and primary health conditions. BPs are formed from amino acids linked by amide bonds and classified by their mode of action in health-related applications. The amino acid composition and their secondary structure determines their activity. More specifically, antimicrobial peptides (AMPs) are used in the development of novel antibacterial agents. The short killing time of the host pathogen with the use of BPs makes it difficult for pathogens to develop resistance in the cells. C18 is an AMP belonging to the cecropin family which I modified for evaluation as a potential therapeutic agent to treat severe methicillin resistant S. aureus (MRSA) infections via reverse sequencing and peptide stapling to enhance its compacity to penetrate lipid interfaces, improve helicity, and metabolic stability. Preliminary results support that these new BPs are antibacterial agents for further development to treat severe MRSA infections. The chemistry and biological assay results of synthesized peptides submitted for evaluation will be discussed in greater detail. Secondly, peripherin 2 (PRPH2) is a photoreceptor specific glycoprotein essential for proper formation of the rod and cone photoreceptor outer segments of the retina, which are the organelles responsible for visual transduction. Defective or absent PRPH2 protein results in various blinding retina diseases such as macular degeneration and retinitis pigmentosa (RP), which range in severity and time of onset. There is currently no known treatment for PRPH2 associated diseases. Therefore, the aim of this second peptide synthesis project is to ultimately develop a shorter drug lead for PRPH2 specific to a conserved region within the C-terminal domain. This region is flexible, functions as a signal sequence for localizing PRPH2 protein to the rod outer segment, critical in membrane fusion, disc morphogenesis, and disc shedding. Truncation and sequence reversal was performed to create thirteen new sequences that may penetrate lipid interfaces more efficiently or possibly function as a cleaved peptide while retaining its function as a shorter drug lead for further drug development for visual transduction. The chemistry and bioassay results for the synthesized peptides will be evaluated as this project is ongoing.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Houston

Year dc:date.issued

2024

Author dc:creator

• Carty, Symone Louise

Advisor dc:contributor.advisor

• Gilbertson, Scott

Committee members dc:contributor.committeemember

• May, Jeremy
• Cai, Chengzhi
• Zastrow, Melissa
• Das, Joydip

• peptides, C18, microwave, reverse sequencing, ring closing metathesis, stapled antimicrobial peptides, RDS, PRPH2, photoreceptors, ROM-1

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10657/17650

OAI identifier oai:identifier

oai:uh-ir.tdl.org:10657/17650