Cyanopeptides: A New and Nearly Inexhaustible Natural Resource for the Design and Structure-Activity Relationship Studies of New Inhibitors of Trypsin-like Serine Proteases

Radau, Gregor

doi:10.2174/157340805774580510

Cited by 12 publications

(10 citation statements)

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“…Serine proteases regulate important biological processes and are attractive targets in therapy (Radau, 2005). Serine protease inhibitors are important in the treatment of a wide variety of human diseases (Rubin, 1996; Leung et al ., 2000; Groll et al ., 2009).…”

Section: Discussionmentioning

confidence: 99%

The non‐ribosomal assembly and frequent occurrence of the protease inhibitors spumigins in the bloom‐forming cyanobacterium Nodularia spumigena

Fewer¹,

Jokela²,

Rouhiainen³

et al. 2009

Molecular Microbiology

138

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SummaryNodularia spumigena is a filamentous nitrogen-fixing cyanobacterium that forms toxic blooms in brackish water bodies worldwide. Spumigins are serine protease inhibitors reported from a single strain of N. spumigena isolated from the Baltic Sea. These linear tetrapeptides contain non-proteinogenic amino acids including a C-terminal alcohol derivative of arginine. However, very little is known about these compounds despite the ecological importance of N. spumigena. We show that spumigins are assembled by two non-ribosomal peptide synthetases encoded in a 21 kb biosynthetic gene cluster. The compact non-ribosomal peptide synthetase features a reductive loading and release mechanism. Our analyses demonstrate that the bulk of spumigins produced by N. spumigena are released as peptide aldehydes in contrast to earlier findings. The main spumigin E variant contains an argininal residue and is a potent trypsin inhibitor. Spumigins were present in all of the N. spumigena strains isolated from the Baltic Sea and comprised up to 1% of the dry weight of the cyanobacterium. Our results demonstrate that bloom-forming N. spumigena strains produce a cocktail of enzyme inhibitors, which may explain in part the ecological success of this cyanobacterium in brackish water bodies worldwide.

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Section: Discussionmentioning

confidence: 99%

The non‐ribosomal assembly and frequent occurrence of the protease inhibitors spumigins in the bloom‐forming cyanobacterium Nodularia spumigena

Fewer¹,

Jokela²,

Rouhiainen³

et al. 2009

Molecular Microbiology

138

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“…The class of Ahp cyclodepsipeptides has entered the focus of researchers due to the intriguing mode-of-action displayed by its members: the Ahp cyclodepsipeptides have been shown to specifically and potently inhibit S1 (trypsin- and chymotrypsin-like) serine proteases in a non-covalent manner [ 54 , 55 , 56 ]. As a consequence, the Ahp cyclodepsipeptides have been suggested as possible leads for the development of novel protease inhibitors [ 57 ].…”

Section: Syntheses Of 3-amino-6-hydroxy-2-piperidone (Ahp) Cyclodementioning

confidence: 99%

Case Studies of the Synthesis of Bioactive Cyclodepsipeptide Natural Products

Stolze

Kaiser

2013

Molecules

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Cyclodepsipeptide natural products often display intriguing biological activities that along with their complex molecular scaffolds, makes them interesting targets for chemical synthesis. Although cyclodepsipeptides feature highly diverse chemical structures, their synthesis is often associated with similar synthetic challenges such as the establishment of a suitable macrocyclization methodology. This review therefore compiles case studies of synthetic approaches to different bioactive cyclodepsipeptide natural products, thereby illustrating obstacles of cyclodepsipeptide synthesis as well as their overcomings.

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“…Since many digestive enzymes such as trypsin and chymotrypsin are serine proteases and are inhibited by these compounds, these natural products could function as digestion inhibitors [ 28 ]. Serine protease inhibitors also cooccur with microcystins and are linked to an enhanced toxin activity or thought to upregulate biosynthetic genes [ 29 ]. The tropical sea urchin Diadema antillarum , which is a cyanobacterium, produces a wide array of serine protease inhibitors including lyngbyastatins 4–6 [ 30 , 31 ], pompanopeptin A [ 32 ], and largamides D–G [ 33 ].…”

Section: Intramolecular Modulation Of Serine Protease Inhibitor Acmentioning

confidence: 99%

Exploring Marine Cyanobacteria for Lead Compounds of Pharmaceutical Importance

Uzair

Tabassum

Rasheed

et al. 2012

The Scientific World Journal

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The Ocean, which is called the “mother of origin of life,” is also the source of structurally unique natural products that are mainly accumulated in living organisms. Cyanobacteria are photosynthetic prokaryotes used as food by humans. They are excellent source of vitamins and proteins vital for life. Several of these compounds show pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immunodeficiency syndrome (AIDS), arthritis, and so forth, while other compounds have been developed as analgesics or to treat inflammation, and so forth. They produce a large variety of bioactive compounds, including substances with anticancer and antiviral activity, UV protectants, specific inhibitors of enzymes, and potent hepatotoxins and neurotoxins. Many cyanobacteria produce compounds with potent biological activities. This paper aims to showcase the structural diversity of marine cyanobacterial secondary metabolites with a comprehensive coverage of alkaloids and other applications of cyanobacteria.

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Cyanopeptides: A New and Nearly Inexhaustible Natural Resource for the Design and Structure-Activity Relationship Studies of New Inhibitors of Trypsin-like Serine Proteases

Cited by 12 publications

References 0 publications

The non‐ribosomal assembly and frequent occurrence of the protease inhibitors spumigins in the bloom‐forming cyanobacterium Nodularia spumigena

The non‐ribosomal assembly and frequent occurrence of the protease inhibitors spumigins in the bloom‐forming cyanobacterium Nodularia spumigena

Case Studies of the Synthesis of Bioactive Cyclodepsipeptide Natural Products

Exploring Marine Cyanobacteria for Lead Compounds of Pharmaceutical Importance

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