Peptide leucine arginine, a potent immunomodulatory peptide isolated and structurally characterized from the skin of the Northern Leopard frog, Rana pipiens

On the basis of histamine release from rat peritoneal mast cells, an octade capeptide was isolated from the skin extract of the Northern Leopard frog ( Rana pipiens), This peptide was purified to homogeneity using reversed-phas e high performance liquid chromatography and found to have the following pr imary structure by Edman degradation and pyridylethylation: LVRGCWTKSYPPKPC FVR, in which Cys(5) and Cys(15) are disulfide bridged. The peptide was nam ed peptide leucine-arginine (pLR), reflecting the N- and C-terminal residue s. Molecular modeling predicted that pLR possessed a rigid tertiary loop st ructure with flexible end regions, pLR was synthesized and elicited rapid, noncytolytic histamine release that had a a-fold greater potency when compa red with one of the most active histamine-liberating peptides, namely melit tin, pLR was able to permeabilize negatively charged unilamellar lipid vesi cles but not neutral vesicles, a finding that was consistent with its nonhe molytic action, pLR inhibited the early development of granulocyte macropha ge colonies from bone marrow stem cells but did not induce apoptosis of the end stage granulocytes, i,e. mature neutrophils, pLR therefore displays bi ological activity with both granulopoietic progenitor cells and mast cells and thus represents a novel bioactive peptide from frog skin.