Presenting Author Hampden-Sydney Chesapeake, Virginia, United States
Ryan Yeates (Hampden-Sydney )| Paul Mueller (Hampden-Sydney College)| Timothy Reichart (Hampden-Sydney College)
Immunoglobulin A (IgA) is an important antibody within the human body’s immune response and comprises over 90% of the upper and lower respiratory immune systems (Chi et al., 2017). The bacterial pathogens such as Hemophilus influenzae, Neisseria gonorrhea, Neisseria meningitides, and Streptococcus pneumonia function to inactivate IgA1 through the production of a high molecular weight proteinase called IgA1P (Burton et al., 1988). Inhibitors of bacterial IgA1 proteinases are being researched as a method to enhance the activity of naturally occurring IgA1 and as an alternative to antibacterials (Burton et al., 1989). Three inhibitors of specifically the IgA1P of Hemophilus influenzae were designed and tested through docking studies with Autodock and HPEPDOCK software. The pentapeptide inhibitors, as opposed to Burton’s tetrapeptide inhibitors, of this variant of IgA1P were based on the hinge-region of IgA1 found in the Hemophilus influenzae variant instead of the Neisseria gonorrhoeae variant. These inhibitors were found to successfully bind to the active site of IgA1P through trials ran with the docking programs. Inhibitor evaluation was supported by looking at values of compounds known to bind to the active site and values of randomly constructed peptides. The inhibitor peptides of PSPST, SPSTP, and TPSPS were found suitable as potential inhibitors to IgA1P and were synthesized using Solid Phase Peptide Synthesis. After the synthesis of the inhibitors, an inhibitory assay was implemented to assess the effectiveness of the synthesized inhibitors. The results allowed for physical confirmations to be made on the effectiveness of the designed inhibitors and whether they would have any merit to compete with the hinge-region peptide for medical use.