Molecular cloning and chemical synthesis of a novel antibacterial peptide derived from pig myeloid cells.
A group of myeloid precursors of defense peptides has recently been shown to have highly homologous N-terminal regions. Using a strategy based on this homology, a novel cDNA was cloned from pig bone marrow RNA and found to encode a 153-residue polypeptide. This comprises a highly conserved region encompassing a 29-residue signal peptide and a 101-residue prosequence, followed by a unique, 23-residue, cationic, C-terminal sequence. A peptide corresponding to this C-terminal sequence was chemically synthesized and shown to exert antimicrobial activity against both Gram positive and negative bacteria at concentrations of 2-16 microM. The activity of this potent and structurally novel antibacterial peptide appears to be mediated by its ability to damage bacterial membranes, as shown by the rapid permeabilization of the inner membrane of Escherichia coli.
Zanetti
M
M
Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, AREA Science Park, Padriciano, Trieste, Italy.
Storici
P
P
Tossi
A
A
Scocchi
M
M
Gennaro
R
R
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000378:metabolism* / Q000633:toxicity; D023181:Antimicrobial Cationic Peptides; D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers; D004926:Escherichia coli / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D010455:Peptides / Q000138:chemical synthesis* / Q000633:toxicity; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013552:Swine
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; D010455:Peptides; C086301:porcine myeloid antibacterial peptide 23