Abstract 1641 Synthesizing Novel Antimicrobial Peptides from H3 and H4 Histone Subunits

Histone-derived antimicrobial peptides (HDAPs) are antimicrobial peptides (AMPs) derived from the sequences of the DNA-binding histone proteins found in eukaryotic cells. Naturally occurring and engineered HDAPs have presented a range of antimicrobial mechanisms across several bacterial species. Buforin II, derived from the histone H2A subunit, is the most thoroughly-characterized HDAP whose mechanism of action involves translocating across bacterial cell membranes and disrupting essential intracellular mechanisms. In fact, most known HDAPs are derived from the histone H2A subunit, while only a few studies have examined the activity or mechanism of action of HDAPs deriving from other histone proteins. Here, we characterize the antimicrobial potential of 20-amino acid-long, staggered fragments of histone H3 and H4 subunits. Preliminary results have identified two particularly active regions of the H3 histone against E. coli and B. subtilis. These active sequences are cationic and include proline residues found in many other active HDAPs. In fact, one sequence has the greatest number of proline residues out of the total HDAP sequences studied. Ongoing studies are investigating the mechanisms of action for these novel H3-derived peptides and are considering the activity of H4 fragments.