With few BI-87G3 exceptions, HDPs are amphipathic, positively charged, and contain a high number of hydrophobic residues. Based on their molecular properties and structural conformations, HDPs can be divided into several classes of which cathelicidins and defensins are the largest and best described. The pig has a large reservoir of cathelicidins relative to other mammals. Based on their primary amino acid compositions, porcine cathelicidins fall into three subgroups: linear proline-rich cathelicidins, disulfide-rich protegrins 1�C5, and a arginine/histidine rich myeloid subgroup. PR-39 was originally isolated from porcine small intestine, but subsequent cDNA cloning showed that PR-39 is also expressed in bone marrow and neutrophils. PR-39 is secreted as a prepropeptide that undergoes post-translational modification by the cleavage of the N-terminal portion releasing the mature form of 39 C-terminal amino acids. This mature PR-39 is active against a broad spectrum of bacteria, including multidrug resistant clinical isolates. Similar to other proline-rich peptides, PR-39 does not only promote cell lysis by membrane perturbation, but translocates across the membrane and disrupts various cellular processes such as DNA and protein NPD4456 synthesis. Besides its antimicrobial properties, PR-39 has been shown-to induce migration of neutrophils in a calcium dependent manner, to modulate macrophage viability by inhibiting apoptosis, and to function as an anti-apoptotic factor in endothelial cells during hypoxia. Many other biological processes such as regulation of angiogenesis, promotion of wound repair, and prevention of inflammation during tissue injury have also been reported. The antimicrobial potential of PR-39 in vivo was elegantly demonstrated in a study where transgenic mice, expressing PR-39, were protected against Group A Streptococcus compared to the control group, although it is not clear whether this was achieved through direct or indirect effects of PR- 39 on bacterial viability and virulence.In this study we seek to find core elements of PR-39 involved in antimicrobial activity and immunomodulation.