FALL-39, A PUTATIVE HUMAN PEPTIDE ANTIBIOTIC, IS CYSTEINE-FREE AND EXPRESSED IN BONE-MARROW AND TESTIS

PR-39, a proline/arginine-rich peptide antibiotic, has been purified f rom pig intestine and later shown to originate in the bone marrow. Int ending to isolate a clone for a human counterpart to PR-39, we synthes ized a PCR probe derived from the PR 39 gene. However, when this probe was used to screen a human bone marrow cDNA library, eight clones wer e obtained with information for another putative human peptide antibio tic, designated FALL-39 after the first four residues. FALL-39 is a 39 -residue peptide lacking cysteine and tryptophan. All human peptide an tibiotics previously isolated (or predicted) belong to the defensin fa mily and contain three disulfide bridges. The clone for prepro-FALL-39 encodes a cathelin-like precursor protein with 170 amino acid residue s, We have postulated a dibasic processing site for the mature FALL-39 and chemically synthesized the putative peptide. In basal medium E, s ynthetic FALL-39 was highly active against Escherichia coil and Bacill us megaterium. Residues 13-34 in FALL-39 can be predicted to form a pe rfect amphiphatic helix, and CD spectra showed that medium E induced 3 0% helix formation in FALL-39. RNA blot analyses disclosed that the ge ne for FALL-39 is expressed mainly in human bone marrow and testis.