title: Therapeutic potential of the peptide leucine arginine as a new nonplant bowman-birk-like serine protease inhibitor.
abstract: The peptide leucine arginine (pLR) belongs to a new class of cyclic peptides isolated from frog skin. Its primary sequence is similar to the reactive loop of plant Bowman-Birk inhibitors (BBI), and the recently discovered circular sunflower trypsin inhibitor-1 (SFTI-1). The conformational properties of pLR in solution were determined by NMR spectroscopy and revealed excellent structural similarity to BBI and SFTI-1. Moreover, pLR is a highly potent trypsin inhibitor, with Ki values in the nanomolar range, and, due to its small size, a potential inhibitor of the serine protease tryptase. Since tryptase plays a crucial role in the development of allergic airway inflammation, the therapeutic potential of pLR in a murine asthma model was investigated. Treatment of ovalbumin-sensitized mice with pLR during allergen challenge reduced the acute asthma phenotype. Most importantly, application even at the end of a long-lasting chronic asthma model decreased the development of chronic airway inflammation and tissue remodeling.
authors.affiliation: Interdisciplinary Center of Clinical Research, University of Leipzig , Leipzig, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Rothemund
authors.forename: Frank D
authors.initials: FD
authors.lastname: Sönnichsen
authors.forename: Tobias
authors.initials: T
authors.lastname: Polte
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D028421:Isoprostanes / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000737:chemistry / Q000494:pharmacology*; D053802:Tryptases / Q000378:metabolism
chemical_list: D028421:Isoprostanes; D010455:Peptides; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; C425308:peptide leucine arginine; D053802:Tryptases