Showing papers on "Antimicrobial peptides published in 1988"

Antimicrobial activity of synthetic magainin peptides and several analogues

Abstract: We have previously reported the isolation of two broad-spectrum antimicrobial peptides ("magainins") from the skin of the African clawed frog Xenopus laevis. These natural peptides are active against many species of bacteria and fungi and also induce osmotic lysis of protozoa. In this report we demonstrate that synthetic magainin peptides appear to be indistinguishable from the natural products with respect to chromatographic properties and biological activity. These studies demonstrate conclusively that the magainin peptides are potent antimicrobial substances.

The Magainins: sequence factors relevant to increased antimicrobial activity and decreased hemolytic activity.

Abstract: The Magainins, two antimicrobial peptides found in the skin of the frog Xenopus laevis, and 50 Magainin analogs were synthesized by the method of simultaneous multiple peptide synthesis (SMPS). This series of peptides was prepared in order to examine the effects of omitting individual amino acids on antimicrobial activity. The series consisted of 22 Magainin 1 omission analogs having a C-terminal carboxyl (M1-C) and 23 Magainin 2 omission analogs having a C-terminal amide (M2-A), as well as both the C-terminal amide and carboxyl forms of Magainin 1 and Magainin 2. These peptides were tested against E. coli (Gram negative), S. epidermis (Gram positive) and C. albicans (yeast). Amino acid omissions in the N-terminal region (residues 1-14) resulted in the complete loss of antimicrobial activity in both Magainin series. These analogs also had very low hemolytic activity against human erythrocytes. However, analogs with omissions in the C-terminal region, especially residues alanine-15, glycine-18 or glutamic acid-19, while having equal or increased antimicrobial activity relative to the original Magainin 1 or Magainin 2 forms, had variable hemolytic action. Thus, both Magainin 1 and Magainin 2 with the glutamic acid 19 omission had equal activity against E. coli and increased activity against S. epidermis, while having lower hemolytic activity than the original sequences. The amide form of Magainin 2 with glycine 18 omitted had equal antimicrobial activity, but significantly increased hemolytic activity. The C-terminal carboxyl form of Magainin 1, however, showed equal antimicrobial activity, but substantially decreased hemolytic action.(ABSTRACT TRUNCATED AT 250 WORDS)

Antifungal Mechanisms of Leukocytes

Abstract: The ablity of phagocytic leukocytes to kill ingested microorganisms arises from two general mechanisms. One of these depends on the phagocyte's ablity to assemble and activate a multicomponent oxidase system that generates superoxide anion (O-2) by oxidizing its substrate, NADPH. The resultant superoxide anions are converted to other reactive oxygen derivatives (RODs), whose precise chemical nature is influenced by the biochemical composition of the phagocyte. In normal human neutrophils (PMN), these secondary RODs include H2O2, hydroxyl radical, hypochlorous acid and chloramines, all of which are considerably more microbicidal than superoxide itself.In addition to undergoing an oxidative attack by RODs, ingested microbes are exposed to antimicrobial constituents normally contained within the phagocyte's cytoplasmic granules. Among these antimicrobial factors are cathepsin G and “defensins”. The microbicidal activity of cathepsin G against bacteria and Candida species occurs independently of its neutral protease activity. Defensins are a recently-defined family of antimicrobial peptides whose members appear to be important effectors of ROD-independent antimicrobial activity by PMN and certain macrophages. The activity spectrum of human and rabbit defensins encompasses both gram-positive and gram-negative bacteria, many fungi, certain viruses and even tumor cells. Defensins constitute 30-50% of the total protein in azurophil granules and account for approximately 6% of the total protein in human PMNs. They exert potent activity against C. albicans, an important agent of opportunistic fungal infection. Human defensins permeabilize microbial membranes, but only the bioenergized membranes of metabolically active microbial targets appear to be susceptible to these effects.Although the clinical syndromes associated with deficiencies of myeloperoxidase and NADPH oxidase activity have been recognized for several years, abnormalities of leukocyte defensins and cathepsin G have been detected only recently. Neutrophils from patients with “specific granule deficiency” lack defensins, whereas PMN in Chediak-Higashi syndrome are deficient in neutral proteases, including cathepsin G.