Structure activity relationship studies on the antimicrobial activity of novel edeine A and D analogues

Czajgucki, Zbigniew; Andruszkiewicz, Ryszard; Kamysz, Wojciech

doi:10.1002/psc.775

Cited by 21 publications

(16 citation statements)

References 20 publications

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“…It was previously demonstrated that the presence of the free ionizable carboxyl group in the (2R,6S,7R)-A 2 ha moiety was not essential for the biological activity of edeines [20,21]. As a continuation of our research project [22], we recently synthesized the following edeine antibiotic analogues ( Compounds 1-4 were shown to exhibit significantly diminished antibacterial and antifungal activities [22], and they did not display toxic effects towards mammalian cells [23]. Initial studies on the immunological effect of edeine, performed in the mid seventies [9,11] demonstrated their suppressive actions in the models of the humoral and cellular immune responses of mice in vivo.…”

Section: Introductionmentioning

confidence: 66%

“…That effect could be due to the direct binding of LPS by highly basic edeine molecules. It is also evident that the substantial decrease in the antibacterial and antifungal activity [22] correlated with the acquisition of interesting immunomodulatory properties (this article). In conclusion, some of the peptides deserve further studies in other experimental models, which could reveal potential therapeutic benefit.…”

Section: Cellular and Molecular Biology Letters 159mentioning

confidence: 81%

“…Cyclosporin A (CsA) was from Sandimmun (Neoral, Sandoz, Basel, Switzerland) in ampoules, edeine B sulphate (peptide W1) from Gdańsk University of Technology (Gdańsk, Poland), RPMI-1640 medium from Cibi/Life Technologies (UK), and FCS-fetal calf serum from Gibco. Peptides 1-4 were synthesized according to the recently described procedure [22].…”

Section: Animals and Reagentsmentioning

confidence: 99%

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The immunoregulatory effects of edeine analogues in mice

Czajgucki¹,

Zimecki²,

Andruszkiewicz³

2007

Cellular and Molecular Biology Letters

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Abstract:The edeines analogs were tested in several in vitro and in vivo assays using the mouse model, with edeine B (peptide W1) and cyclosporine A as reference compounds. The peptides displayed moderate, stimulatory effects on concanavalin A-induced (ConA-induced) splenocyte proliferation, whereas their effects on pokeweed mitogen-induced (PWM-induced) splenocyte proliferation were inhibitory. The peptides inhibited lipopolysacharide-induced (LPSinduced) tumor necrosis factor alpha production but had little effect on interleukin 6 production. In the model of the humoral immune response in vitro to sheep red blood cells, peptide 1 was distinctly stimulatory in the investigated concentrations (1-100 μg/ml), whereas peptides 3 and 4 only stimulated the number of antibody-forming cells at the highest concentration (100 μg/ml). In the model of the delayed type hypersensitivity in vivo to ovalbumin, the peptides were moderately suppressive (3 being the most active). The reference peptide W1 stimulated ConA-induced cell proliferation at 1-10 μg/ml but was inhibitory at 100 μg/ml. It also inhibited PWM-induced cell proliferation in a dosedependent manner. This peptide had no effect on the humoral immune response in vitro or on cytokine production, but inhibited DTH reaction in vivo. The relationship between structure and activity, and a possible mode of action of the peptides, is discussed in this paper.

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Section: Introductionmentioning

confidence: 66%

Section: Cellular and Molecular Biology Letters 159mentioning

confidence: 81%

Section: Animals and Reagentsmentioning

confidence: 99%

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The immunoregulatory effects of edeine analogues in mice

Czajgucki¹,

Zimecki²,

Andruszkiewicz³

2007

Cellular and Molecular Biology Letters

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“…Note that some peptides can show more than one activity. For example, there are 9 curated peptides in the Norine database that present both antibiotic and immunomodulator activities (such as edeines [12]) and 14 didemnins (66) that present three activities, antibiotic, antitumor, and immunomodulator.…”

Section: Study Of Biological Activity (I) Statistical Resultsmentioning

confidence: 99%

Diversity of Monomers in Nonribosomal Peptides: towards the Prediction of Origin and Biological Activity

et al. 2010

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Nonribosomal peptides (NRPs) are molecules produced by microorganisms that have a broad spectrum of biological activities and pharmaceutical applications (e.g., antibiotic, immunomodulating, and antitumor activities). One particularity of the NRPs is the biodiversity of their monomers, extending far beyond the 20 proteogenic amino acid residues. Norine, a comprehensive database of NRPs, allowed us to review for the first time the main characteristics of the NRPs and especially their monomer biodiversity. Our analysis highlighted a significant similarity relationship between NRPs synthesized by bacteria and those isolated from metazoa, especially from sponges, supporting the hypothesis that some NRPs isolated from sponges are actually synthesized by symbiotic bacteria rather than by the sponges themselves. A comparison of peptide monomeric compositions as a function of biological activity showed that some monomers are specific to a class of activities. An analysis of the monomer compositions of peptide products predicted from genomic information (metagenomics and high-throughput genome sequencing) or of new peptides detected by mass spectrometry analysis applied to a culture supernatant can provide indications of the origin of a peptide and/or its biological activity.Nonribosomal peptides (NRPs) are molecules produced by microorganisms and synthesized by huge multienzymatic complexes (38, 41), called nonribosomal peptide synthetases (NRPSs). These megaenzymes are organized into modules, one for each amino acid to be built into the peptide product. This is accomplished by division of each catalytic step into specialized semiautonomous domains. The basic set of domains (adenylation, thiolation, and condensation) within a module can be extended by substrate-modifying domains, including domains for substrate epimerization, ␤ hydroxylation, N methylation, and heterocyclic ring formation. The peptide release is catalyzed by a thioesterase domain which can also, in many cases, be involved in an intramolecular reaction leading to a cyclic or partially cyclic peptide or, in fewer cases, in the oligomerization of peptide units (iterative biosynthesis). NRPs show a broad spectrum of biological activities and pharmaceutical applications. They can harbor antimicrobial, immunomodulator, or antitumor activities. Cyclosporine (5), an immunosuppressant drug widely used in organ transplantation, daptomycin (60) (marketed in the United States under the trade name Cubicin), used in the treatment of certain infections caused by Gram-positive bacteria, aminoadipyl-cysteinylvaline (ACV)-tripeptide, which is the precursor of cephalosporin and penicillin (29), the most famous antibiotic, and also bleomycin (57), used in the treatment of several cancers, are some common examples of NRPs of high therapeutic importance. Two main structural traits distinguish these peptides from ribosomally synthesized peptides: first, their primary structure is more frequently cyclic (partially or totally) branched or polycyclic rather than linear and, seco...

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“…It can secrete large amounts of secondary metabolites, which are important for controlling pathogens. Among them, tyrocidine, gramicidin (4,5,6), gratisin (12), and edeine (1) have been successively isolated and identified. Only recently, the genome of one B. brevis strain, NBRC 100599, is available in the GenBank database (http://www .ncbi.nlm.nih.gov/nuccore/226309587?reportϭGenBank).…”

mentioning

confidence: 99%