Discipline: Chemistry and Chemical Sciences
Subcategory: Biochemistry (not Cell and Molecular Biology and Genetics)
Soijett A. Blue - North Carolina Agricultural and Technical State University
Co-Author(s): Julius Harp, North Carolina Agricultural and Technical State University, Greensboro NC
Low molecular weight peptides are important compounds and are well acknowledged for their pharmacological applications in biological systems. The relevance of this work comes from an executive summary from the CDC in 2013 stating that pathogens are becoming resistant and have the potential to become a worldwide health hazard. The focus of this work involves the synthetic construction of small peptides (i.e., di/tri) that mimic the primary structural framework of known antimicrobial peptides that are incorporated with an alaninic unit (s). Thus, this research pre-validates optimal possibilities of antibiotic activity due to similarities in structures as well as the rational substitutions of novel alaninic (e.g., phenylalaninic) moieties within the resulting peptide. This research has been successful in the synthesis of three phenylalaninic (i.e., phenylalanine-type) amino acids, and our laboratory is currently exploring the rational synthesis and design of relevant di/tri-peptides. This work also seeks to explore structure and activity profile building by utilizing small cyclic peptides. Small peptides that contain cyclic unit are known to be rigid which facilitates receptor binding selectivity which translates into pharmacological specificity. In addition, di/tri peptides that consists of cyclic units are known to be resistant to enzymatic degradation due to the inhibition of hydrolytic breakdown, which typically begins at the C- or N-termini of the peptide unit. Protection of the C- or N- terminus will be constructed by utilizing protection methods such as Fluorenylmethyloxycarbonyl chloride (FMOC) or tert-butyloxycarbonyl (BOC) for the C- and N- terminus, respectively. After the novel amino acid is synthesized then an appropriate de-protection method will be utilized. Cyclic peptides can be constructed by the rational use of bridging molecular units. Thus, additional synthetic design will focus on electronic and physical shielding moieties, which will be incorporated into the framework of the peptides in order to increase carbonyls stability towards chymotryptic degradation. The resulting novel peptides will be tested for inhibition against various bacteria along with an appropriate control reference by utilizing Minimum Inhibition Concentration Assay. The ultimate resolution of this work lends application to the development of antimicrobial peptide that display optimal efficacy toward resistant microbial strains.Not Submitted
Funder Acknowledgement(s): I would like to acknowledge and thank NSF and NC-LSAMP Bridge to the Doctorate Fellowship for funding my research.
Faculty Advisor: Julius Harp, email@example.com