The
peptide antibiotic PR-39 was originally isolated from the upper part of pig intestine. It has antibacterial activity against Gram negative bacteria at concentrations comparable with
tetracycline. Studies of the mechanism of action showed that
PR-39 inhibits both
DNA and
protein synthesis. Recently,
PR-39 was found in
wound fluid and was shown to have inductive activity on matrix components as part of the
wound repair process. We have now sequenced the complete gene and possible mediators of its expression will be discussed. Our attempts to characterize the human counterpart of
PR-39 by probing for the well conserved prepro-part led to a different
peptide antibiotic. A clone containing the coding information for this new
peptide was isolated from a human bone marrow cDNA library. The putative human
peptide antibiotic was designated
FALL-39 after the first four residues and the total number of residues. All human
peptide antibiotics previously isolated (or predicted) belong to the
defensin family with three
disulfide bridges, while
FALL-39 lacks
cysteine. The clone for the prepro-FALL-39 encodes a
cathelin-like precursor
protein with 170
amino acid residues. We have postulated a dibasic processing site for the mature
FALL-39 and chemically synthesized the
peptide. In the presence of the basal medium E, synthetic
FALL-39 was highly active against Escherichia coli D21 and Bacillus megaterium Bm11. Residues 13-34 in
FALL-39 can be predicted to form a perfect amphipatic helix and CD spectra showed that medium E induced 30% helix formation in
FALL-39. By Northern blot analyses the transcript was located in bone marrow and testis. The structure of the gene and the chromosomal location is under investigation.