LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity

We report the isolation and characterization of a novel human peptide with antimicrobial activity, termed LEAP-1 (liver-expressed antimicrobial peptid e). Using a mass spectrometric assay detecting cysteine-rich peptides, a 25 -residue peptide containing four disulfide bonds was identified in human bl ood ultrafiltrate, LEAP-1 expression was predominantly detected in the live r, and, to a much lower extent, in the heart. In radial diffusion assays, G ram-positive Bacillus megaterium, Bacillus subtilis, Micrococcus luteus, St aphylococcus carnosus, and Gram-negative Neisseria cinerea as well as the y east Saccharomyces cerevisiae dose-dependently exhibited sensitivity upon t reatment with synthetic LEAP-1, The discovery of LEAP-1 extends the known f amilies of mammalian peptides with antimicrobial activity by its novel disu lfide motif and distinct expression pattern. (C) 2000 Federation of Europea n Biochemical Societies, Published by Elsevier Science B.V. All rights rese rved.