The Isolation and Structure Elucidation of Tasiamide B, a 4-Amino-3-hydroxy-5-phenylpentanoic Acid Containing Peptide from the Marine Cyanobacterium <i>Symploca </i>sp.

Williams, Philip G.; Yoshida, Wesley Y.; Moore, Richard E.; Paul, Valerie J.

doi:10.1021/np030114z

Cited by 70 publications

(48 citation statements)

References 15 publications

(22 reference statements)

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“…Other structurally related cyanobacterial compounds include grassystatin C ( 3 ), 9 bearing a Leu-derived statine core, and tasiamide E ( 4 ) and tasiamide ( 5 ) which lack the statine unit (Figure 2). 10,11,19 …”

Section: Resultsmentioning

confidence: 99%

“…Grassystatins A–C, bearing a Leu-derived statine core, isolated from Lyngbya cf. confervoides , were found to be potent inhibitors of cathepsins D and E. 9 On the other hand, tasiamide B ( 2 ), containing a Phe-derived statine unit, isolated from the marine cyanobacterium Symploca sp., 10,11 was found to inhibit β-site amyloid precursor protein cleaving enzyme 1 (BACE1) in addition to cathepsins D and E. 12 The dysregulated activity of aspartic proteases has been associated with several diseases, and these proteases may represent important therapeutic targets. BACE1 for instance, is a potential therapy target for Alzheimer’s disease (AD) as it has been shown to cleave amyloid precursor protein (APP) resulting in the generation and accumulation of amyloid β-peptide (Aβ) in the brain, a key player in the pathogenesis of AD.…”

Section: Introductionmentioning

confidence: 99%

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Tasiamide F, a potent inhibitor of cathepsins D and E from a marine cyanobacterium

Al-Awadhi

Ratnayake

Paul

et al. 2016

Bioorganic & Medicinal Chemistry

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In search of novel protease inhibitors with therapeutic potential, our efforts exploring the marine cyanobacterium Lyngbya sp. have led to the discovery of tasiamide F (1), which is an analogue of tasiamide B (2). The structure was elucidated using a combination of NMR spectroscopy and mass spectrometry. The key structural feature in 1 is the presence of the Phe-derived statine core, which contributes to its aspartic protease inhibitory activity. The antiproteolytic activity of 1 and 2 was evaluated in vitro against cathepsins D and E, and BACE1. Tasiamide F (1) displayed IC50 values of 57 nM, 23 nM, and 0.69 μM, respectively, indicating greater selectivity for cathepsins over BACE1 compared with tasiamide B (2). Molecular docking experiments were carried out for compounds 1 and 2 against cathepsins D and E to rationalize their activity towards these proteases. The dysregulated activities of cathepsins D and E have been implicated in cancer and regulation of immune responses, respectively, and these proteases represent potential therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tasiamide F, a potent inhibitor of cathepsins D and E from a marine cyanobacterium

Al-Awadhi

Ratnayake

Paul

et al. 2016

Bioorganic & Medicinal Chemistry

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“…Additionally, tasiamide and tasiamide B both showed moderate cytotoxicity against KB cells, with IC 50 values of 0.48 and 0.8 μM, respectively. 19,24 Due to limited isolated quantities of tasiamide E ( 3 ), only tasiamides C ( 1 ) and D ( 2 ) were evaluated for their cytotoxicity against the HCT-116 colon cancer cell line and were found to be inactive (tasiamide C, IC 50 > 25 μM; tasiamide D, IC 50 ≈ 25 μM).…”

Section: Resultsmentioning

confidence: 99%

Lipopeptides from the Tropical Marine Cyanobacterium Symploca sp.

et al. 2014

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A collection of the tropical marine cyanobacterium Symploca sp., collected near Kimbe Bay, Papua New Guinea, previously yielded several new metabolites including kimbeamides A–C, kimbelactone A, and tasihalide C. Investigations into a more polar cytotoxic fraction yielded three new lipopeptides, tasiamides C–E (1–3). The planar structures were deduced by 2D NMR spectroscopy and tandem mass spectrometry, and their absolute configurations were determined by a combination of Marfey’s and chiral-phase GC-MS analysis. These new metabolites are similar to several previously isolated compounds, including tasiamide (4), grassystatins (5, 6), and symplocin A, all of which were isolated from similar filamentous marine cyanobacteria.

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“…Like the grassystatins, the phenylstatine-bearing peptide tasiamide B 158,159 (Fig. 11) also exhibited aspartic protease inhibitory activity but with a different selectivity profile.…”

Section: Mechanisms Of Action and Direct Cellular Targets Of Biologmentioning

confidence: 99%

Biological targets and mechanisms of action of natural products from marine cyanobacteria

2015

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Marine cyanobacteria are an ancient group of organisms and prolific producers of bioactive secondary metabolites. These compounds are presumably optimized by evolution over billions of years to exert high affinity for their intended biological target in the ecologically relevant organism but likely also possess activity in different biological contexts such as human cells. Screening of marine cyanobacterial extracts for bioactive natural products has largely focused on cancer cell viability; however, diversification of the screening platform led to the characterization of many new bioactive compounds. Targets of compounds have oftentimes been elusive if the compounds were discovered through phenotypic assays. Over the past few years, technology has advanced to determine mechanism of action (MOA) and targets through reverse chemical genetic and proteomic approaches, which has been applied to certain cyanobacterial compounds and will be discussed in this review. Some cyanobacterial molecules are the most-potent-in-class inhibitors and therefore may become valuable tools for chemical biology to probe protein function but also be templates for novel drugs, assuming in vitro potency translates into cellular and in vivo activity. Our review will focus on compounds for which the direct targets have been deciphered or which were found to target a novel pathway, and link them to disease states where target modulation may be beneficial.

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The Isolation and Structure Elucidation of Tasiamide B, a 4-Amino-3-hydroxy-5-phenylpentanoic Acid Containing Peptide from the Marine Cyanobacterium Symploca sp.

Cited by 70 publications

References 15 publications

Tasiamide F, a potent inhibitor of cathepsins D and E from a marine cyanobacterium

Tasiamide F, a potent inhibitor of cathepsins D and E from a marine cyanobacterium

Lipopeptides from the Tropical Marine Cyanobacterium Symploca sp.

Biological targets and mechanisms of action of natural products from marine cyanobacteria

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