PR-39, A PROLINE-RICH PEPTIDE ANTIBIOTIC FROM PIG, AND FALL-39, A TENTATIVE HUMAN COUNTERPART

The peptide antibiotic PR-39 was originally isolated from the upper pa rt of pig intestine. It has antibacterial activity against Gram negati ve bacteria at concentrations comparable with tetracycline. Studies of the mechanism of action showed that PR-39 inhibits both DNA and prote in synthesis. Recently, PR-39 was found in wound fluid and was shown t o have inductive activity on matrix components as part of the wound re pair process, We have now sequenced the complete gene and possible med iators of its expression will be discussed, Our attempts to characteri ze the human counterpart of PR-39 by probing for the well conserved pr epro-part led to a different peptide antibiotic. A clone containing th e coding information for this new peptide was isolated from a human bo ne marrow cDNA library. The putative human peptide antibiotic was desi gnated FALL-39 after the first four residues and the total number of r esidues. All human peptide antibiotics previously isolated (or predict ed) belong to the defensin family with three disulfide bridges, while FALL-39 lacks cysteine, The clone for the prepro-FALL-39 encodes a cat helin-like precursor protein with 170 amino acid residues, We have pos tulated a dibasic processing site for the mature FALL-39 and chemicall y synthesized the peptide. In the presence of the basal medium E, synt hetic FALL-39 was highly active against Escherichia coli D21 and Bacil lus megaterium Bm11. Residues 13-34 in FALL-39 can be predicted to for m a perfect amphipatic helix and CD spectra showed that medium E induc ed 30% helix formation in FALL-39. By Northern blot analyses the trans cript was located in bone marrow and testis, The structure of the gene and the chromosomal location is under investigation.