HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krause, A. Articles by Adermann, K. Search for Related Content PubMed PubMed Citation Articles by Krause, A. Articles by Adermann, K. Social Bookmarking                   What's this?

Isolation and biochemical characterization of LEAP-2, a novel blood peptide expressed in the liver

¹ IPF PharmaCeuticals GmbH, Hannover, Germany
² Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
³ BioVisioN AG, Hannover, Germany
⁴ Ingenium Pharmaceuticals AG, Martinsried, Germany

The human genome contains numerous genes whose protein products are unknown in terms of structure, interaction partner, expression, and function. To unravel the function of these orphan genes, it is of particular value to isolate native forms of protein and peptide products derived from these genes. From human blood ultrafiltrate, we characterized a novel gene-encoded, cysteine-rich, and cationic peptide that we termed liver-expressed antimicrobial peptide 2 (LEAP-2). We identified several circulating forms of LEAP-2 differing in their amino-terminal length, all containing a core structure with two disulfide bonds formed by cysteine residues in relative 1–3 and 2–4 positions. Molecular cloning of the cDNA showed that LEAP-2 is synthesized as a 77-residue precursor, which is predominantly expressed in the liver and highly conserved among mammals. This makes it a unique peptide that does not exhibit similarity with any known human peptide regarding its primary structure, disulfide motif, and expression. Analysis of the LEAP-2 gene resulted in the identification of an alternative promoter and at least four different splicing variants, with the two dominating transcripts being tissue-specifically expressed. The largest native LEAP-2 form of 40 amino acid residues is generated from the precursor at a putative cleavage site for a furin-like endoprotease. In contrast to smaller LEAP-2 variants, this peptide exhibited dose-dependent antimicrobial activity against selected microbial model organisms. LEAP-2 shares some characteristic properties with classic peptide hormones and it is expected that the isolation of this novel peptide will help to unravel its physiological role.

Keywords: Alternative splicing; antimicrobial activity; disulfide bonds; hemofiltrate; liver; peptide; secretion

Abbreviations: CFU, colony-forming unit • ESIMS, electrospray ionization mass spectrometry • LEAP, liver-expressed antimicrobial peptide • RT-PCR, reverse transcription/polymerase chain reaction • TFA, trifluoroacetic acid

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Motzkus, S. Schulz-Maronde, A. Heitland, A. Schulz, W.-G. Forssmann, M. Jubner, and E. Maronde The novel {beta}-defensin DEFB123 prevents lipopolysaccharide-mediated effects in vitro and in vivo FASEB J, August 1, 2006; 20(10): 1701 - 1702. [Abstract] [Full Text] [PDF]

				E. Eriste, A. Norberg, D. Nepomuceno, C. Kuei, F. Kamme, D.-T. Tran, K. Strupat, H. Jornvall, C. Liu, T. W. Lovenberg, et al. A Novel Form of Neurotensin Post-translationally Modified by Arginylation J. Biol. Chem., October 21, 2005; 280(42): 35089 - 35097. [Abstract] [Full Text] [PDF]

				C. L. Townes, G. Michailidis, C. J. Nile, and J. Hall Induction of Cationic Chicken Liver-Expressed Antimicrobial Peptide 2 in Response to Salmonella enterica Infection Infect. Immun., December 1, 2004; 72(12): 6987 - 6993. [Abstract] [Full Text] [PDF]