Marine Drugs

858 KiB

Open AccessArticle

Functional Expression in Escherichia coli of the Disulfide-Rich Sea Anemone Peptide APETx2, a Potent Blocker of Acid-Sensing Ion Channel 3

by Raveendra Anangi, Lachlan D. Rash, Mehdi Mobli and Glenn F. King

Mar. Drugs 2012, 10(7), 1605-1618; https://doi.org/10.3390/md10071605 - 23 Jul 2012

Cited by 26 | Viewed by 7865

Abstract

Acid-sensing ion channels (ASICs) are proton-gated sodium channels present in the central and peripheral nervous system of chordates. ASIC3 is highly expressed in sensory neurons and plays an important role in inflammatory and ischemic pain. Thus, specific inhibitors of ASIC3 have the potential [...] Read more.

Acid-sensing ion channels (ASICs) are proton-gated sodium channels present in the central and peripheral nervous system of chordates. ASIC3 is highly expressed in sensory neurons and plays an important role in inflammatory and ischemic pain. Thus, specific inhibitors of ASIC3 have the potential to be developed as novel analgesics. APETx2, isolated from the sea anemone Anthopleura elegantissima, is the most potent and selective inhibitor of ASIC3-containing channels. However, the mechanism of action of APETx2 and the molecular basis for its interaction with ASIC3 is not known. In order to assist in characterizing the ASIC3-APETx2 interaction, we developed an efficient and cost-effective Escherichia coli periplasmic expression system for the production of APETx2. NMR studies on uniformly ¹³C/¹⁵N-labelled APETx2 produced in E. coli showed that the recombinant peptide adopts the native conformation. Recombinant APETx2 is equipotent with synthetic APETx2 at inhibiting ASIC3 channels expressed in Xenopus oocytes. Using this system we mutated Phe15 to Ala, which caused a profound loss of APETx2’s activity on ASIC3. These findings suggest that this expression system can be used to produce mutant versions of APETx2 in order to facilitate structure-activity relationship studies. Full article

(This article belongs to the Special Issue Sea Anemone Toxins)

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Open AccessReview

Exploiting the Nephrotoxic Effects of Venom from the Sea Anemone, Phyllodiscus semoni, to Create a Hemolytic Uremic Syndrome Model in the Rat

by Masashi Mizuno, Yasuhiko Ito and B. Paul Morgan

Mar. Drugs 2012, 10(7), 1582-1604; https://doi.org/10.3390/md10071582 - 23 Jul 2012

Cited by 19 | Viewed by 10859

Abstract

In the natural world, there are many creatures with venoms that have interesting and varied activities. Although the sea anemone, a member of the phylum Coelenterata, has venom that it uses to capture and immobilise small fishes and shrimp and for protection [...] Read more.

In the natural world, there are many creatures with venoms that have interesting and varied activities. Although the sea anemone, a member of the phylum Coelenterata, has venom that it uses to capture and immobilise small fishes and shrimp and for protection from predators, most sea anemones are harmless to man. However, a few species are highly toxic; some have venoms containing neurotoxins, recently suggested as potential immune-modulators for therapeutic application in immune diseases. Phyllodiscus semoni is a highly toxic sea anemone; the venom has multiple effects, including lethality, hemolysis and renal injuries. We previously reported that venom extracted from Phyllodiscus semoni induced acute glomerular endothelial injuries in rats resembling hemolytic uremic syndrome (HUS), accompanied with complement dysregulation in glomeruli and suggested that the model might be useful for analyses of pathology and development of therapeutic approaches in HUS. In this mini-review, we describe in detail the venom-induced acute renal injuries in rat and summarize how the venom of Phyllodiscus semoni could have potential as a tool for analyses of complement activation and therapeutic interventions in HUS. Full article

(This article belongs to the Special Issue Sea Anemone Toxins)

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2045 KiB

Open AccessArticle

Lochmolins A–G, New Sesquiterpenoids from the Soft Coral Sinularia lochmodes

by Yen-Ju Tseng, Kuo-Ping Shen, Hui-Li Lin, Chiung-Yao Huang, Chang-Feng Dai and Jyh-Horng Sheu

Mar. Drugs 2012, 10(7), 1572-1581; https://doi.org/10.3390/md10071572 - 20 Jul 2012

Cited by 26 | Viewed by 6969

Abstract

Seven new sesquiterpenoids, lochmolins A–G (1–7), were isolated from a Taiwanese soft coral Sinularia lochmodes. The structures of these metabolites were elucidated by extensive spectroscopic study. Compounds 1–4 were found to inhibit the accumulation of the [...] Read more.

Seven new sesquiterpenoids, lochmolins A–G (1–7), were isolated from a Taiwanese soft coral Sinularia lochmodes. The structures of these metabolites were elucidated by extensive spectroscopic study. Compounds 1–4 were found to inhibit the accumulation of the LPS-induced pro-inflammatory COX-2 protein in RAW264.7 macrophage cells. Full article

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181 KiB

Open AccessArticle

Pseudoalteromone B: A Novel 15C Compound from a Marine Bacterium Pseudoalteromonas sp. CGH2XX

by Yu-Hsin Chen, Jimmy Kuo, Jui-Hsin Su, Tsong-Long Hwang, Yung-Husan Chen, Chia-Hung Lee, Ching-Feng Weng and Ping-Jyun Sung

Mar. Drugs 2012, 10(7), 1566-1571; https://doi.org/10.3390/md10071566 - 20 Jul 2012

Cited by 10 | Viewed by 6068

Abstract

A novel 15C compound, pseudoalteromone B (1), possessing a novel carbon skeleton, was obtained from a marine bacterium Pseudoalteromonas sp. CGH2XX. This bacterium was originally isolated from a cultured-type octocoral Lobophytum crassum, that was growing in cultivating tanks equipped with [...] Read more.

A novel 15C compound, pseudoalteromone B (1), possessing a novel carbon skeleton, was obtained from a marine bacterium Pseudoalteromonas sp. CGH2XX. This bacterium was originally isolated from a cultured-type octocoral Lobophytum crassum, that was growing in cultivating tanks equipped with a flow-through sea water system. The structure of 1 was established by spectroscopic methods. Pseudoalteromone B (1) displayed a modestly inhibitory effect on the release of elastase by human neutrophils. Full article

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Open AccessArticle

Atypical Reactive Center Kunitz-Type Inhibitor from the Sea Anemone Heteractis crispa

by Irina Gladkikh, Margarita Monastyrnaya, Elena Leychenko, Elena Zelepuga, Victoria Chausova, Marina Isaeva, Stanislav Anastyuk, Yaroslav Andreev, Steve Peigneur, Jan Tytgat and Emma Kozlovkaya

Mar. Drugs 2012, 10(7), 1545-1565; https://doi.org/10.3390/md10071545 - 19 Jul 2012

Cited by 21 | Viewed by 8388

Abstract

The primary structure of a new Kunitz-type protease inhibitor InhVJ from the sea anemone Heteractis crispa (Radianthus macrodactylus) was determined by protein sequencing and cDNA cloning. InhVJ amino acid sequence was shown to share high sequence identity (up to 98%) with [...] Read more.

The primary structure of a new Kunitz-type protease inhibitor InhVJ from the sea anemone Heteractis crispa (Radianthus macrodactylus) was determined by protein sequencing and cDNA cloning. InhVJ amino acid sequence was shown to share high sequence identity (up to 98%) with the other known Kunitz-type sea anemones sequences. It was determined that the P1 Thr at the reactive site resulted in a decrease of the K_i of InhVJ to trypsin and α-chymotrypsin (7.38 × 10⁻⁸ M and 9.93 × 10⁻⁷ M, respectively). By structure modeling the functional importance of amino acids at the reactive site as well as at the weak contact site were determined. The significant role of Glu45 for the orientation and stabilization of the InhVJ-trypsin complex was elucidated. We can suggest that there has been an adaptive evolution of the P1 residue at the inhibitor reactive site providing specialization or functional diversification of the paralogs. The appearance of a key so-called P1 Thr residue instead of Lys might lead to refinement of inhibitor specificity in the direction of subfamilies of serine proteases. The absence of Kv channel and TRPV1-receptor modulation activity was confirmed by electrophysiological screening tests. Full article

(This article belongs to the Special Issue Sea Anemone Toxins)

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Open AccessArticle

4-Methylenesterols from a Sponge Theonella swinhoei

by Jheng-Kun Guo, Ching-Ying Chiang, Mei-Chin Lu, Wen-Been Chang and Jui-Hsin Su

Mar. Drugs 2012, 10(7), 1536-1544; https://doi.org/10.3390/md10071536 - 19 Jul 2012

Cited by 17 | Viewed by 7582

Abstract

Three new 4-methylenesterols, theonellasterol K (1), acetyltheonellasterol (2) and acetyldehydroconicasterol (3), along with two known sterols, theonellasterol (4) and theonellasterone (5), were isolated from the sponge Theonella swinhoei. The structures of these [...] Read more.

Three new 4-methylenesterols, theonellasterol K (1), acetyltheonellasterol (2) and acetyldehydroconicasterol (3), along with two known sterols, theonellasterol (4) and theonellasterone (5), were isolated from the sponge Theonella swinhoei. The structures of these compounds were elucidated on the basis of their spectroscopic data and comparison of the NMR data with those of known analogues. Compound 1 exhibited significant cytotoxic activity against HCT-116, K562 and Molt 4 cancer cell lines. Full article

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1672 KiB

Open AccessArticle

Paralemnolide A, an Unprecedented Bisnorsesquiterpene from the Taiwanese Soft Coral Paralemnalia thyrsoides

by Shang-Kwei Wang, Yu-Sheng Lee and Chang-Yih Duh

Mar. Drugs 2012, 10(7), 1528-1535; https://doi.org/10.3390/md10071528 - 17 Jul 2012

Cited by 16 | Viewed by 7063

Abstract

Paralemnolide A (1), possessing an unprecedented bisnorsesquiterpene skeleton, was isolated from the soft coral Paralemnalia thyrsoides. The structure of paralemnolide A was elucidated by extensive analysis of spectroscopic data. The anti-HCMV (human cytomegalovirus) activity of 1 and its cytotoxicity against [...] Read more.

Paralemnolide A (1), possessing an unprecedented bisnorsesquiterpene skeleton, was isolated from the soft coral Paralemnalia thyrsoides. The structure of paralemnolide A was elucidated by extensive analysis of spectroscopic data. The anti-HCMV (human cytomegalovirus) activity of 1 and its cytotoxicity against selected cell lines were evaluated. Full article

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Open AccessArticle

Cyclisation Increases the Stability of the Sea Anemone Peptide APETx2 but Decreases Its Activity at Acid-Sensing Ion Channel 3

by Jonas E. Jensen, Mehdi Mobli, Andreas Brust, Paul F. Alewood, Glenn F. King and Lachlan D. Rash

Mar. Drugs 2012, 10(7), 1511-1527; https://doi.org/10.3390/md10071511 - 16 Jul 2012

Cited by 25 | Viewed by 7131

Abstract

APETx2 is a peptide isolated from the sea anemone Anthopleura elegantissima. It is the most potent and selective inhibitor of acid-sensing ion channel 3 (ASIC3) and it is currently in preclinical studies as a novel analgesic for the treatment of chronic inflammatory [...] Read more.

APETx2 is a peptide isolated from the sea anemone Anthopleura elegantissima. It is the most potent and selective inhibitor of acid-sensing ion channel 3 (ASIC3) and it is currently in preclinical studies as a novel analgesic for the treatment of chronic inflammatory pain. As a peptide it faces many challenges in the drug development process, including the potential lack of stability often associated with therapeutic peptides. In this study we determined the susceptibility of wild-type APETx2 to trypsin and pepsin and tested the applicability of backbone cyclisation as a strategy to improve its resistance to enzymatic degradation. Cyclisation with either a six-, seven- or eight-residue linker vastly improved the protease resistance of APETx2 but substantially decreased its potency against ASIC3. This suggests that either the N- or C-terminus of APETx2 is involved in its interaction with the channel, which we confirmed by making N- and C-terminal truncations. Truncation of either terminus, but especially the N-terminus, has detrimental effects on the ability of APETx2 to inhibit ASIC3. The current work indicates that cyclisation is unlikely to be a suitable strategy for stabilising APETx2, unless linkers can be engineered that do not interfere with binding to ASIC3. Full article

(This article belongs to the Special Issue Sea Anemone Toxins)

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Open AccessArticle

Further Insights on the Carotenoid Profile of the Echinoderm Marthasterias glacialis L.

by Lilian R. B. Mariutti, David M. Pereira, Adriana Zerlotti Mercadante, Patrícia Valentão, Natércia Teixeira and Paula B. Andrade

Mar. Drugs 2012, 10(7), 1498-1510; https://doi.org/10.3390/md10071498 - 12 Jul 2012

Cited by 23 | Viewed by 7006

Abstract

In this study, the carotenoid profile of the echinoderm Marthasterias glacialis L. was established using HPLC-DAD-APCI-MS/MS equipped with a C₃₀ column. This approach rendered the identification of 20 compounds, eight of them reported for the first time in this marine organism. Differentiation [...] Read more.

In this study, the carotenoid profile of the echinoderm Marthasterias glacialis L. was established using HPLC-DAD-APCI-MS/MS equipped with a C₃₀ column. This approach rendered the identification of 20 compounds, eight of them reported for the first time in this marine organism. Differentiation of carotenoid isomers was also achieved. Full article

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Open AccessReview

Algal Lectins as Potential HIV Microbicide Candidates

by Dana Huskens and Dominique Schols

Mar. Drugs 2012, 10(7), 1476-1497; https://doi.org/10.3390/md10071476 - 10 Jul 2012

Cited by 79 | Viewed by 10091

Abstract

The development and use of topical microbicides potentially offers an additional strategy to reduce the spread of the Human Immunodeficiency Virus (HIV). Carbohydrate-binding agents (CBAs) that show specificity for high mannose carbohydrates on the surface of the heavily glycosylated envelope of HIV are [...] Read more.

The development and use of topical microbicides potentially offers an additional strategy to reduce the spread of the Human Immunodeficiency Virus (HIV). Carbohydrate-binding agents (CBAs) that show specificity for high mannose carbohydrates on the surface of the heavily glycosylated envelope of HIV are endowed with potent anti-HIV activity. In fact, a number of algal lectins such as cyanovirin-N, microvirin, microcystis viridis lectin, scytovirin, Oscillatoria agardhii agglutinin and griffithsin are considered as potential microbicide candidates to prevent the sexual transmission of HIV through topical applications. They not only inhibit infection of cells by cell-free virus but they can also efficiently prevent virus transmission from virus-infected cells to uninfected CD4⁺ target T-lymphocytes and DC-SIGN-directed capture of HIV-1 and transmission to CD4⁺ T lymphocytes. This review focuses on the structural properties and carbohydrate specificity of these algal lectins, their antiviral activity against HIV and several other enveloped viruses, their safety profile and viral resistance patterns. Full article

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Open AccessArticle

The Use of UV-Visible Reflectance Spectroscopy as an Objective Tool to Evaluate Pearl Quality

by Snezana Agatonovic-Kustrin and David W. Morton

Mar. Drugs 2012, 10(7), 1459-1475; https://doi.org/10.3390/md10071459 - 10 Jul 2012

Cited by 10 | Viewed by 9543

Abstract

Assessing the quality of pearls involves the use of various tools and methods, which are mainly visual and often quite subjective. Pearls are normally classified by origin and are then graded by luster, nacre thickness, surface quality, size, color and shape. The aim [...] Read more.

Assessing the quality of pearls involves the use of various tools and methods, which are mainly visual and often quite subjective. Pearls are normally classified by origin and are then graded by luster, nacre thickness, surface quality, size, color and shape. The aim of this study was to investigate the capacity of Artificial Neural Networks (ANNs) to classify and estimate the quality of 27 different pearls from their UV-Visible spectra. Due to the opaque nature of pearls, spectroscopy measurements were performed using the Diffuse Reflectance UV-Visible spectroscopy technique. The spectra were acquired at two different locations on each pearl sample in order to assess surface homogeneity. The spectral data (inputs) were smoothed to reduce the noise, fed into ANNs and correlated to the pearl’s quality/grading criteria (outputs). The developed ANNs were successful in predicting pearl type, mollusk growing species, possible luster and color enhancing, donor condition/type, recipient/host color, donor color, pearl luster, pearl color, origin. The results of this study shows that the developed UV-Vis spectroscopy-ANN method could be used as a more objective method of assessing pearl quality (grading) and may become a valuable tool for the pearl grading industry. Full article

(This article belongs to the Special Issue Marine Biomaterials)

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486 KiB

Open AccessArticle

Formamido-Diterpenes from the South China Sea Sponge Acanthella cavernosa

by Ying Xu, Jun-Hui Lang, Wei-Hua Jiao, Ru-Ping Wang, Ying Peng, Shao-Jiang Song, Bao-Hua Zhang and Hou-Wen Lin

Mar. Drugs 2012, 10(7), 1445-1458; https://doi.org/10.3390/md10071445 - 2 Jul 2012

Cited by 17 | Viewed by 7183

Abstract

Seven new formamido-diterpenes, cavernenes A–D (1–4), kalihinenes E and F (5–6), and kalihipyran C (7), together with five known compounds (8–12), were isolated from the South China Sea sponge [...] Read more.

Seven new formamido-diterpenes, cavernenes A–D (1–4), kalihinenes E and F (5–6), and kalihipyran C (7), together with five known compounds (8–12), were isolated from the South China Sea sponge Acanthella cavernosa. Structures were established using IR, HRESIMS, 1D and 2D NMR, and single X-ray diffraction techniques. The isolated compounds were assessed for their cytotoxicity against a small panel of human cancer cell lines (HCT-116, A549, HeLa, QGY-7701, and MDA-MB-231) with IC₅₀ values in the range of 6–18 μM. In addition, compound 9 showed weak antifungal activity against Trichophyton rubrum and Microsporum gypseum with MIC values of 8 and 32 μg/mL, respectively, compound 10 displayed weak antifungal activity against fungi Candida albicans, Cryptococcus neoformans, T. rubrum, and M. gypseum with MIC values of 8, 8, 4, and 8 μg/mL, respectively. Full article

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Open AccessArticle

Three New Cembranoids from the Taiwanese Soft Coral Sarcophyton ehrenbergi

by Shang-Kwei Wang, Mu-Keng Hsieh and Chang-Yih Duh

Mar. Drugs 2012, 10(7), 1433-1444; https://doi.org/10.3390/md10071433 - 27 Jun 2012

Cited by 26 | Viewed by 6495

Abstract

In order to search for new bioactive substances from marine organisms, we have investigated the acetone extracts of the soft coral Sarcophyton ehrenbergi collected at San-Hsian-Tai, Taitong County, Taiwan. Chromatographic fractionation of the extracts of the octocoral S. ehrenbergi led to the [...] Read more.

In order to search for new bioactive substances from marine organisms, we have investigated the acetone extracts of the soft coral Sarcophyton ehrenbergi collected at San-Hsian-Tai, Taitong County, Taiwan. Chromatographic fractionation of the extracts of the octocoral S. ehrenbergi led to the isolation of three new cembranoids, (+)-12-ethoxycarbonyl-11Z-sarcophine (1), ehrenbergol A and B (2 and 3). The structures of these isolated metabolites were elucidated through extensive spectroscopic analyses. Moreover, metabolites 1–3 were evaluated in vitro for their cytotoxicity towards selected cancer cell lines and antiviral activity against human cytomegalovirus (HCMV). Full article

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287 KiB

Open AccessArticle

Polyoxygenated Sterols from the South China Sea Soft Coral Sinularia sp.

by Rui Li, Chang-Lun Shao, Xin Qi, Xiu-Bao Li, Jing Li, Ling-Ling Sun and Chang-Yun Wang

Mar. Drugs 2012, 10(7), 1422-1432; https://doi.org/10.3390/md10071422 - 26 Jun 2012

Cited by 38 | Viewed by 7223

Abstract

Chemical investigation of the ethanol extract of soft coral Sinularia sp. collected from the South China Sea led to the isolation of three new polyoxygenated sterols, (3S,23R,24S)-ergost-5-ene-3β,23α,25-triol (1), (24S)-ergostane-6-acetate-3β,5α,6β,25-tetraol (2), (24 [...] Read more.

Chemical investigation of the ethanol extract of soft coral Sinularia sp. collected from the South China Sea led to the isolation of three new polyoxygenated sterols, (3S,23R,24S)-ergost-5-ene-3β,23α,25-triol (1), (24S)-ergostane-6-acetate-3β,5α,6β,25-tetraol (2), (24S)-ergostane-6-acetate-3β,6β,12β,25-tetraol (3) together with three known ones (4–6). The structures, including relative configurations of the new compounds (1–3), were elucidated by detailed analysis of spectroscopic data (IR, UV, NMR, MS) and by comparison with related reported compounds. The absolute configuration of 1 was further determined by modified Mosher’s method. Compound 5 exhibited moderate cytotoxicity against K562 cell line with an IC₅₀ value of 3.18 μM, but also displayed strong lethality toward the brine shrimp Artemia salina with a LC₅₀ value of 0.96 μM. Full article

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Mar. Drugs, Volume 10, Issue 7 (July 2012) – 14 articles , Pages 1422-1618

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