Miraziridine A, a Novel Cysteine Protease Inhibitor from the Marine Sponge Theonella aff. mirabilis1

Nakao, Yoichi; Fujita, Masaki; Warabi, Kaoru; Matsunaga, Shigeki; Fusetani, Nobuhiro

doi:10.1021/ja001859j

Cited by 91 publications

(66 citation statements)

References 14 publications

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“…The presence of cysteine protease inhibitors in marine invertebrates have been previously reported [53] [54], although this source of biomolecules have been less explored. Recently, a fraction enriched in tight-binding protease inhibitors was isolated from the Caribbean coral P. homomalla showing Falcipain 2 and Cruzipain inhibitory activity at the nanomolar level [55].…”

Section: Discussionmentioning

confidence: 99%

Screening of Protease Inhibitory Activity in Aqueous Extracts of Marine Invertebrates from Cuban Coast

González¹,

Sánchez²,

Rojas³

et al. 2016

AJAC

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Protease inhibitors have been isolated from many variable sources; however, the need to identify and characterize new molecules has increased with the discovery of new therapeutic targets and the lack of specificity of already identified compounds with inhibitory activity. The goal of this work was to search for inhibitory activity against four proteolytic enzymes already recognized as therapeutic targets: human neutrophil elastase, dipeptidyl peptidase IV, subtilisin from Bacillus licheniformis and cathepsin K in selected marine invertebrates from the Caribbean Sea. A systematic screening was carried out with selected aqueous extracts belonging to 20 species from seven different phyla: Annelida, Bryozoa, Chordata, Cnidaria, Equinodermata, Mollusca and Porifera, all collected at the coast of Havana (Cuba). All extracts showing initial inhibitory activity were characterized in terms of IC50 values and specific inhibitory activity (SIA). Model enzymes were used in the case of human neutrophil elastase (porcine pancreatic elastase) and cathepsin K (papain) for the screening and all positive results were confirmed by testing toward the therapeutic targets. Ten extracts were identified showing inhibitory activity against human neutrophil elastase, for which the most promising values were obtained for Nerita peloronta. Only one extract, Bunodosoma granulifera, showed inhibitory activity against dipeptidyl peptidase IV with rather poor values of IC50 and SIA. Seven extracts showed inhibitory activity against B. licheniformis subtilisin with very good IC50 and SIA values for Lissodendorix isodyctialis, Cenchritis muricatus, and N. peloronta. Finally, eight extracts were positive for cathepsin K with almost similar parameters values among them. All these results confirmed the richness and potential of the marine invertebrate's fauna and indicated new promising sources for the identification of natural compounds with potential application in therapeutics.

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Section: Discussionmentioning

confidence: 99%

Screening of Protease Inhibitory Activity in Aqueous Extracts of Marine Invertebrates from Cuban Coast

González¹,

Sánchez²,

Rojas³

et al. 2016

AJAC

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“…[55] In diesem linearen Pentapeptid sind vier der fünf Aminosäuren nichtproteinogen. Neben Aminobuttersäure (Aba), [56] dem nächstlängeren Homologen von Ala, kommen drei bemerkenswerte Bausteine vor: ein Aziridindicarboxylat (Azd), [57] Statin [52] und Vinyl-Arg.…”

Section: Lineare Peptideunclassified

Nichtproteinogene Aminosäurebausteine für Peptidgerüste aus nichtribosomalen Peptiden und hybriden Polyketiden

2013

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Frei vorkommende nichtproteinogene Aminosäuren sind schon lange wegen ihrer antimetabolen Eigenschaften bekannt. Entdeckt werden sie meist aufgrund der Reaktivität gegenüber der katalytischen Wirkung der Zielenzyme. Führt man sie regiospezifisch in biogene Peptide und Proteine ein, kann es möglich werden, eine neue Ära der Medizinalchemie an der Grenze zwischen kleinen und großen Wirkstoffen einzuleiten. Außerdem eröffnet die ortsspezifische Funktionalisierung von Proteinen besonders attraktive Strategien für die posttranslationale Proteinmodifizierung. Auch bieten viele der Aminosäuren, die von der Natur nicht für den Einbau in Proteine ausgewählt wurden, reiche architektonische Möglichkeiten bei Einführung in ribosomal hergestellte Polypeptide. Dieser Aufsatz fasst die Biosynthesewege zu den wichtigsten Klassen nichtkanonischer Bausteine und deren Stoffwechsellogik zusammen, die in nichtribosomalen Peptidgerüsten und nichtribosomalen Peptid‐Polyketid‐Hybriden resultieren.

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“…Miraziridine A 15,16) is a pentapeptide isolated from the marine sponge Theonella aff. mirabilis by Fusetani et al in 2000.…”

Section: Synthesis Of Miraziridine Amentioning

confidence: 99%

“…mirabilis by Fusetani et al in 2000. This natural peptide is composed of (2R,3R)-aziridine-2,3-dicarboxylic acid (Azd), L-leucine (Leu), (3S,4S)-statine (Sta), (S)--aminobutyric acid (Abu), and (S)-vinylogous arginine (vArg).…”

Section: Synthesis Of Miraziridine Amentioning

confidence: 99%

Synthesis of Bioactive Natural Products as Protein Inhibitors

Konno¹

2012

Bioscience, Biotechnology, and Biochemistry

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Miraziridine A, a Novel Cysteine Protease Inhibitor from the Marine Sponge Theonella aff. mirabilis¹

Cited by 91 publications

References 14 publications

Screening of Protease Inhibitory Activity in Aqueous Extracts of Marine Invertebrates from Cuban Coast

Screening of Protease Inhibitory Activity in Aqueous Extracts of Marine Invertebrates from Cuban Coast

Nichtproteinogene Aminosäurebausteine für Peptidgerüste aus nichtribosomalen Peptiden und hybriden Polyketiden

Synthesis of Bioactive Natural Products as Protein Inhibitors

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