New Peptolides from the Cyanobacterium <i>Nostoc insulare</i> as Selective and Potent Inhibitors of Human Leukocyte Elastase

Mehner, Christian; Müller, Daniela; Kehraus, Stefan; Hautmann, Stephanie; Gütschow, Michael; König, Gabriele M.

doi:10.1002/cbic.200800415

Cited by 28 publications

(32 citation statements)

References 51 publications

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“…leucine, isoleucine, or valine. Residue 6 is most often a threonine, with a few reports of β-hydroxy-γ-methyl-proline [65,66]. In either case, the side chain hydroxy of residue 6 is linked, via an ester bond, to carboxylate moiety of the amino acid at residue 5.…”

Section: Protease Inhibitors From Cyanobacteriamentioning

confidence: 99%

Chemodiversity in Freshwater and Terrestrial Cyanobacteria – A Source for Drug Discovery

Chlipala¹,

Mo²,

Orjala³

2011

CDT

117

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Cyanobacteria are considered a promising source for new pharmaceutical lead compounds and a large number of chemically diverse and bioactive metabolites have been obtained from cyanobacteria over the last few decades. This review highlights the structural diversity of natural products from freshwater and terrestrial cyanobacteria. The review is divided into three areas: cytotoxic metabolites, protease inhibitors, and antimicrobial metabolites. The first section discusses the potent cytotoxins cryptophycin and tolytoxin. The second section covers protease inhibitors from freshwater and terrestrial cyanobacteria and is divided in five subsections according to structural class: aeruginosins, cyanopeptolins, microviridins, anabaenopeptins, and microginins. Structure activity relationships are discussed within each protease inhibitor class. The third section, antimicrobial metabolites from freshwater and terrestrial cyanobacteria, is divided by chemical class in three subsections: alkaloids, peptides and terpenoids. These examples emphasize the structural diversity and drug development potential of natural products from freshwater and terrestrial cyanobacteria.

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Section: Protease Inhibitors From Cyanobacteriamentioning

confidence: 99%

Chemodiversity in Freshwater and Terrestrial Cyanobacteria – A Source for Drug Discovery

Chlipala¹,

Mo²,

Orjala³

2011

CDT

117

View full text Add to dashboard Cite

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“…As elastase specifically interacts with substrates containing smaller and hydrophobic residues, it has more specificity with the A–D peptides rather than homophenylalanine containing E–F peptides. From SAR of insulapeptolides, it can be understood that L‐ N,O ‐dimethyl‐tyrosine, Ahp and Hmp moieties along with other hydrophobic amino acid residues are the crucial structural units for elastase inhibition (Mehner et al ., ).…”

Section: Protease Inhibitorsmentioning

confidence: 99%

SAR analysis and bioactive potentials of freshwater and terrestrial cyanobacterial compounds: a review

Nagarajan

Maruthanayagam

Sundararaman

2012

J of Applied Toxicology

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Freshwater and terrestrial cyanobacteria resemble the marine forms in producing divergent chemicals such as linear, cyclic and azole containing peptides, alkaloids, cyclophanes, terpenes, lactones, etc. These metabolites have wider biomedical potentials in targeting proteases, cancers, parasites, pathogens and other cyanobacteria and algae (allelopathy). Among the various families of non-marine cyanobacterial peptides reported, many of them are acting as serine protease inhibitors. While the micropeptin family has a preference for chymotrypsin inhibition rather than other serine proteases, the aeruginosin family targets trypsin and thrombin. In addition, cyanobacterial compounds such as scytonemide A, lyngbyazothrins C and D and cylindrocyclophanes were found to inhibit 20S proteosome. Apart from proteases, metabolites blocking the other targets of cancer pathways may exhibit cytotoxic effect. Colon and rectum, breast, lung and prostate are the worst affecting cancers in humans and are deduced to be inhibited by both peptidic and non-peptidic compounds. Moreover, the growth of infections causing parasites such as Plasmodium, Leishmania and Trypanosoma are well controlled by peptides: aerucyclamides A-D, tychonamides and alkaloids: nostocarboline and calothrixins. Likewise, varieties of cyanobacterial compounds tend to inhibit serious infectious disease causing bacterial, fungal and viral agents. Interestingly, portoamides, spiroidesin, nostocyclamide and kasumigamide are the allelopathic peptides determined to suppress the growth of toxic cyanobacteria and nuisance algae. Thus cyanobacterial compounds have a broad bioactive spectrum; the analysis of SAR studies will not only assist to find out the mode of action but also reveal bioactive key components. Thereby, developing the drugs bearing these bioactive skeletons to treat various illnesses is wide open.

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“…In such NRPS peptide families, structurally related amino acids, such as Val, Ile, and Leu, are found in equivalent positions of the peptides, suggesting that the A domains of these NRPS enzymes may possess a relaxed substrate specificity (19). Since in principle each A domain involved in biosynthesis could have such a relaxed specificity, the producer organism may be able to generate a true natural combinatorial library with a diversity limited by the number of A domains that display relaxed substrate specificity for structurally related amino acids, e.g., as observed for the insulapeptolides (29).…”

mentioning

confidence: 99%

Genetic Variation of Adenylation Domains of the Anabaenopeptin Synthesis Operon and Evolution of Substrate Promiscuity

et al. 2011

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New Peptolides from the Cyanobacterium Nostoc insulare as Selective and Potent Inhibitors of Human Leukocyte Elastase

Cited by 28 publications

References 51 publications

Chemodiversity in Freshwater and Terrestrial Cyanobacteria – A Source for Drug Discovery

Chemodiversity in Freshwater and Terrestrial Cyanobacteria – A Source for Drug Discovery

SAR analysis and bioactive potentials of freshwater and terrestrial cyanobacterial compounds: a review

Genetic Variation of Adenylation Domains of the Anabaenopeptin Synthesis Operon and Evolution of Substrate Promiscuity

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