Solid‐phase synthesis of PYLa and isolation of its natural counterpart, PGLa [PYLa‐(4–24)] from skin secretion of Xenopus laevis

Andreu, David; Aschauer, Harald; Kreil, Günther; Merrifield, R. B.

doi:10.1111/j.1432-1033.1985.tb08957.x

Cited by 83 publications

(33 citation statements)

References 23 publications

(22 reference statements)

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“…Granular glands in the skin of X. laevis produce bioactive peptides, including antimicrobial peptides (1,16,17,23,25,32,40,57,60,70). The contents of the glands are secreted onto the surface of the skin after stimulation of the local sympathetic nerves, which might occur as a result of injury or alarm (2,13,19,58).…”

Section: Resultsmentioning

confidence: 99%

Immune Defenses againstBatrachochytrium dendrobatidis, a Fungus Linked to Global Amphibian Declines, in the South African Clawed Frog,Xenopus laevis

et al. 2010

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Batrachochytrium dendrobatidis is a chytrid fungus that causes the lethal skin disease chytridiomycosis in amphibians. It is regarded as an emerging infectious disease affecting diverse amphibian populations in many parts of the world. Because there are few model amphibian species for immunological studies, little is known about immune defenses against B. dendrobatidis. We show here that the South African clawed frog, Xenopus laevis, is a suitable model for investigating immunity to this pathogen. After an experimental exposure, a mild infection developed over 20 to 30 days and declined by 45 days postexposure. Either purified antimicrobial peptides or mixtures of peptides in the skin mucus inhibited B. dendrobatidis growth in vitro. Skin peptide secretion was maximally induced by injection of norepinephrine, and this treatment resulted in sustained skin peptide depletion and increased susceptibility to infection. Sublethal X-irradiation of frogs decreased leukocyte numbers in the spleen and resulted in greater susceptibility to infection. Immunization against B. dendrobatidis induced elevated pathogen-specific IgM and IgY serum antibodies. Mucus secretions from X. laevis previously exposed to B. dendrobatidis contained significant amounts of IgM, IgY, and IgX antibodies that bind to B. dendrobatidis. These data strongly suggest that both innate and adaptive immune defenses are involved in the resistance of X. laevis to lethal B. dendrobatidis infections.Batrachochytrium dendrobatidis is a newly described chytrid fungus that causes the lethal skin disease chytridiomycosis in amphibians (29). Growing evidence links amphibian declines in Australia, Central America, the western United States, Europe, and Africa to this emerging infectious disease (4, 9, 12, 26, 29, 34-36, 45, 65). B. dendrobatidis colonizes skin cells of adults and the keratinized mouth parts of tadpoles (3, 4, 29, 34) but does not invade other tissues. It is spread by waterborne zoospores that attach to the skin and migrate to the basal layer of the epidermis (3). The pathogen replicates within the epidermal cells and moves to the surface as the cells mature. Emerging zoospores may infect the same host or another nearby host (3,4,29,34). Recent evidence supports the hypothesis that death results from impaired retention of essential ions by the skin resulting in eventual cardiac arrest (63, 64). Some species of amphibians are very resistant to lethal infections of B. dendrobatidis, whereas others are more susceptible (4,26,27,38,(66)(67)(68), and the factors that determine resistance or susceptibility are not well understood. Although much is known about amphibian immunity in general (9, 14, 41), there is limited information about specific immune responses against B. dendrobatidis.We hypothesized that resistant species have antimicrobial peptides or antibodies in the mucus that limit initial infections by B. dendrobatidis zoospores and prevent the further colonization of the same host by zoospores emerging from the skin. Previous work has shown th...

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Section: Resultsmentioning

confidence: 99%

Immune Defenses againstBatrachochytrium dendrobatidis, a Fungus Linked to Global Amphibian Declines, in the South African Clawed Frog,Xenopus laevis

et al. 2010

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“…PGLB is an actual example of how a dibasic site was initially guessed to be the processing site in a precursor which was deduced from a cDNA sequence [61]. When the peptide was eventually isolated and sequenced, it turned out that the conversion took place at a monobasic site three residues further down the precursor ( fig.1) [36].…”

Section: Problems In Predicting Posttranslational Modifications From mentioning

confidence: 99%

The processing of peptide precursors

Schwartz

1986

FEBS Letters

230

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The classical conversion site in precursors of regulatory peptides is a sequence of two basic amino acids. During recent years, however, a group of monobasic cleavage sites has emerged. In certain cell systems it has been shown that the monobasic cleavage mechanism is both a specific mechanism which only attacks a particular basic residue, and a distinct mechanism which can be separated from the dibasic cleaving mechanism within the same cell. The vast majority of monobasic cleavages occur at single arginines although cleavage after a lysine residue has also been demonstrated. There is no ‘consensus sequence’ of amino acids surrounding the single basic residue which is the apparent signal for proteolytic processing. However, in approximately one third of the cases, a proline residue is found either just before or just after the basic residue. On the basis of this ‘proline‐directed arginyl cleavage’ it is discussed how the conformation of the peptide backbone might be important for this type of cleavage. Finally, it is suggested that tissue‐specific expression of different processing enzymes, e.g. dibasic and monobasic specific forms, might explain the tissue‐specific processing of precursors like the pro‐opiomelanocortin and the CKK. and somatostatin precursor.

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“…Thus cecropin A (CA), the first insect antibacterial peptide to be reported [8] and a rather potent antibiotic, has a linear but relatively long (37-residue) sequence which, though clearly accessible through chemical synthesis [9], is not an ideal candidate for drug development. PGL ", PYL" [10,11] and other antibiotical peptides from amphibian skin such as the magalnins [3] are smaller in size and thus less demanding synthetically [12], but somewhat less effective as antibiotics than the cecropins. Defensins [6], on the other hand, while showing interesting antibacterial, antifungal and antiviral properties, are rather complex, highly folded structures with three internal disulfide bonds and have so far proved rather difficult to prepare by chemical means [13].…”

Section: Introductionmentioning

confidence: 99%

Shortened cecropin A‐melittin hybrids Significant size reduction retains potent antibiotic activity

et al. 1992

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We have earlier reported two 26‐residue antibacterial peptides made up from different segments ol'cecropin A (CA) and melittin (M). We now report a substantial reduction in size at the C‐terminal section of the highly active hybrid CA(1–8)M(1–18), leading to a series of 20‐, 18‐ and 15‐residue analogs with antibiotic properties similar to the larger molecule. In particular, the 15‐residue hybrids CA(1–7)M(2–9), CA(1–7)M(4–11) and CA(1–7)M(5–12) are the shortest cecropin‐based peptide antibiotics described so far, with antibacterial activity and spectra similar or better than cecropin A and a 60% reduction in size. Their reduced size and highly α‐helical structure require an alternative mechanism for their interaction with bacterial membranes.

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Solid‐phase synthesis of PYL^a and isolation of its natural counterpart, PGL^a [PYL^a‐(4–24)] from skin secretion of Xenopus laevis

Cited by 83 publications

References 23 publications

Immune Defenses againstBatrachochytrium dendrobatidis, a Fungus Linked to Global Amphibian Declines, in the South African Clawed Frog,Xenopus laevis

Immune Defenses againstBatrachochytrium dendrobatidis, a Fungus Linked to Global Amphibian Declines, in the South African Clawed Frog,Xenopus laevis

The processing of peptide precursors

Shortened cecropin A‐melittin hybrids Significant size reduction retains potent antibiotic activity

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