Japanese Sea Hare Research Articles

Synthesis and Late-Stage Modification of (-)-Doliculide Derivatives Using Matteson's Homologation Approach.

(-)-Doliculide, a marine cyclodepsipeptide derived from the Japanese sea hare, Dolabella auricularia, exhibits potent cytotoxic properties, sparking interest in the field of synthetic chemistry. It is comprised of a peptide segment and a polyketide moiety, rendering it amenable to Matteson's homologation methodology. This technique facilitates the diversification of the distinctive polyketide side chain, thereby permitting the introduction of functional groups in late stages for modifications of the derived compounds and studies on structure-activity relationships.

Aplyronines D–H from the sea hare Aplysia kurodai: isolation, structures, and cytotoxicity

Five cytotoxic macrolides, aplyronines D–H ( 4– 8), were isolated from the Japanese sea hare Aplysia kurodai. They are new congeners of the antitumor compound aplyronine A ( 1), which was previously isolated from the same organism. Their structures were determined by spectroscopic analysis (NMR and MS). The cytotoxicity of these new compounds was evaluated in comparison with that of aplyronines A–C ( 1– 3), suggesting the importance of the 7- O-seryl ester group for mediating the potent cytotoxicity of aplyronines.

Cytotoxicity and Glycan-Binding Profile of a d-Galactose-Binding Lectin from the Eggs of a Japanese Sea Hare (Aplysia kurodai)

A divalent cation-independent 16 kDa D-galactose binding lectin (AKL-2) was isolated from eggs of sea hare, Aplysia kurodai. The lectin recognized D-galactose and D-galacturonic acid and had a 32 kDa dimer consisting of two disulfide-bonded 16 kDa subunits. Eighteen N-terminus amino acids were identified by Edman degradation, having unique primary structure. Lectin blotting analysis with horseradish peroxidase-conjugated lectins has shown that AKL-2 was a glycoprotein with complex type oligosaccharides with N-acetyl D-glucosamine and mannose at non-reducing terminal. Two protein bands with 38 and 36 kDa in the crude extract of sea hare eggs after purification of the lectin was isolated by AKL-2-conjugated Sepharose column and elution with 0.1 M lactose containing buffer. It suggested that the lectin binds with an endogenous ligand in the eggs. AKL-2 kept extreme stability on haemagglutination activity if it was treated at pH 3 and 70 °C for 1 h. Glycan binding profile of AKL-2 by frontal affinity chromatography technology using 15 pyridylamine labeled oligosaccharides has been appeared that the lectin uniquely recognized globotriose (Galα1-4Galβ1-4Glc; Gb3) in addition to bi-antennary complex type N-linked oligosaccharides with N-acetyllactosamine. Surface plasmon resonance analysis of AKL-2 against a neo-glycoprotein, Gb3-human serum albumin showed the k(ass) and k(diss) values are 2.4 × 10³ M⁻¹ s⁻¹ and 3.8 × 10⁻³ s⁻¹, respectively. AKL-2 appeared cytotoxicity against both Burkitt's lymphoma Raji cell and erythroleukemia K562. The activity to Raji by the lectin was preferably cancelled by the co-presence of melibiose mimicing Gb3. On the other hand, K562 was cancelled effectively by lactose than melibiose. It elucidated that AKL-2 had cytotoxic ability mediated glycans structure to cultured cells.

ChemInform Abstract: Synthesis of Dolastatin I, a Cytotoxic Cyclic Hexapeptide from the Sea Hare Dolabella auricularia.

Abstract Dolastatin I, a cytotoxic cyclic hexapeptide isolated from the Japanese sea hare Dolabella auricularia , was enantioselectively synthesized, which confirmed its stereostructure.

Purification and biochemical characterization of a D-galactose binding lectin from Japanese sea hare (Aplysia kurodai) eggs

A lectin was purified from Japanese sea hare Aplysia kurodai by lactosyl-agarose affinity chromatography. The molecular mass of the lectin was determined to be 56 and 32 kDa by SDS-PAGE under non-reducing and reducing conditions, respectively. It was found to agglutinate trypsinized and glutaraldehyde-fixed rabbit and human erythrocytes in the absence of divalent cations. The lectin exhibited stable thermo-tolerance as it retained hemagglutinating activity for 1 h even at 80 degrees C and showed stability at pH 10. By contrast, it was very sensitive at pH less than 5 and in the presence of the sulfhydryl-group preserving reagent, beta-mercaptoethanol. The hemagglutinating activity by the lectin was specifically inhibited by D-galactose, galacturonic acid, methyl-alpha- and methyl-beta-D-galactopyranoside, lactose, melibiose, and asialofetuin. The association rate constant (k(ass)) and dissociation rate constant (k(diss)) were determined for the lectin to be 4.3 x 10(5) M(-1) x sec(-1) and 2.2 x 10(-3) sec(-1), respectively, using a surface plasmon resonance biosensor. The lectin moderately inhibited cell proliferation in the P388 cell line dose dependently. Interestingly, lectin-treated cells did not show a fragmented DNA ladder as is caused by apoptosis, suggesting that the cell proliferation inhibition was caused by another unknown mechanism.

Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia: isolation, structure determination, synthesis, and biological activity

The bioassay-guided fractionation of the cytotoxic constituents of the Japanese sea hare Dollabella auricularia led to the isolation of aurilide ( 1 ), a 26-membered cyclodepsipeptide. The gross structure of 1 was established by spectroscopic analysis including 2D NMR techniques. The absolute stereostructure was determined by chiral HPLC analysis of acid hydrolysates of 1 and by the enantioselective synthesis of a degradation product arising from a dihydroxylated fatty acid portion. The enantioselective synthesis of 1 was achieved in 12% overall yield (16 steps) and confirmed the absolute stereostructure of 1 . The cytotoxicity of 1 was evaluated using a synthetic sample, which was found to exhibit potent cytotoxicity against HeLa S 3 cells with an IC 50 of 0.011 μg/mL. Further biological and pharmacological studies of 1 have been carried out by using synthetic 1 .

ChemInform Abstract: Auriculol, a Cytotoxic Oxygenated Squalene from the Japanese Sea Hare Dolabella auricularia: Isolation, Stereostructure, and Synthesis.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Auriculol, a cytotoxic oxygenated squalene from the Japanese sea hare Dolabella auricularia: isolation, stereostructure, and synthesis

Auriculol, a cytotoxic oxygenated squalene, was isolated from the Japanese sea hare Dolabella auricularia, and its stereostructure was elucidated by spectral analysis and organic synthesis.

Aplysiallene, a new bromoallene as an Na, K-ATPase inhibitor from the sea hare, Aplysia kurodai.

A new bromoallene metabolite, named aplysiallene, was isolated from the Japanese sea hare, Aplysia kurodai, as an Na, K-ATPase inhibitor. Its structure was elucidated by spectroscopic methods. The known metabolites, laurinterol and debromolaurinterol, isolated from this animal were also evaluated for their Na, K-ATPase inhibitory activity.

Synthesis of dolastatin I, a cytotoxic cyclic hexapeptide from the sea hare Dolabella auricularia

Dolastatin I, a cytotoxic cyclic hexapeptide isolated from the Japanese sea hare Dolabella auricularia, was enantioselectively synthesized, which confirmed its stereostructure.

Isolation and stereostructure of dolastatin I, a cytotoxic cyclic hexapeptide from the Japanese sea hare Dolabella auricularia

Dolastatin I (1), a cyclic hexapeptide containing three kinds of five-membered heterocycles (oxazole, thiazole, and oxazoline), has been isolated from the Japanese sea hare Dolabella auricularia. The gross structure of 1 was elucidated by spectroscopic analysis. The absolute stereostructure of 1 was determined by chiral HPLC analysis of the amino acid components obtained by acid hydrolysis of 1. Dolastatin I (1) exhibited cytotoxicity against HeLa S3 cells with an IC50 value of 12 μg/mL.

Dolabelides C and D, Cytotoxic Macrolides Isolated from the Sea Hare Dolabella auricularia

Two new cytotoxic 24-membered macrolides, dolabelides C and D, were isolated from the Japanese sea hare Dolabella auricularia. Their gross structures were deduced by spectroscopic analysis including the 2D NMR technique, and their absolute stereochemistry was determined by means of chemical correlation with the known dolabelide A. Dolabelides C and D exhibited cytotoxicities against HeLa S3 cells with IC50 values of 1.9 and 1.5 μg/mL, respectively.

Isolation and stereostructure of aurilide, a novel cyclodepsipeptide from the Japanese sea hare Dolabella auricularia

Aurilide ( 1), a new 26-membered cyclodepsipeptide, has been isolated from the Japanese sea hare Dolabella auricularia. The gross structure of 1 was established by spectroscopic analysis. The absolute stereostructure of 1 was determined by HPLC analysis of amino acid components and isoleucic acid obtained from acidic hydrolysis of 1 and by the enantioselective synthesis of the tris( p-bromobenzoate) 3 derived from the dihydroxy acid moiety.

Synthesis of dolastatin G and nordolastatin G, cytotoxic 35-membered cyclodepsipeptides of marine origin

The synthesis of dolastatin G ( 1) and nordolastatin G ( 2), new cytotoxic cyclodepsipeptides from the Japanese sea hare Dolabella auricularia, was achieved enantioselectively, and the present result confirmed their stereostructures unambiguously.

Aurisides A and B, Cytotoxic Macrolide Glycosides from the Japanese Sea Hare Dolabella auricularia.

Bioassay-guided fractionation of the cytotoxic constituents of the Japanese sea hare Dolabella auricularia led to the isolation of two novel cytotoxic compounds, aurisides A (1) and B (2). Their gross structures were established by spectroscopic analysis including the 2D NMR technique. On the basis of the NOESY spectral analysis and the degradation experiments, their absolute stereostructures were determined to be 14-membered macrolide glycosides that contain a bromine-substituted conjugated diene structure, a cyclic hemiacetal moiety, and a 2,4-di-O-methyl-L-rhamnopyranoside part. Aurisides A (1) and B (2) show cytotoxicity against HeLa S(3) cells with IC(50) values of 0.17 and 1.2 &mgr;g/mL, respectively.

Isolation and Stereostructures of Dolastatin G and Nordolastatin G, Cytotoxic 35-Membered Cyclodepsipeptides from the Japanese Sea Hare Dolabella auricularia.

A bioassay-directed fractionation of the cytotoxic constituents of the Japanese sea hare Dolabella auricularia resulted in the isolation of two 35-membered depsipeptides dolastatin G (1) and nordolastatin G (2), which showed cytotoxicity against HeLa S(3) cells with IC(50) values of 1.0 and 5.3 &mgr;g/mL, respectively. The gross structures of these substances were established by spectroscopic analysis including 2D NMR techniques. The absolute stereostructure of 1 was determined by chiral HPLC analysis of amino acid components obtained from acid hydrolysis of 1 and by the enantioselective syntheses of two degradation products arising from polyketide portions. Nordolastatin G (2) is a congener that has the same absolute stereochemistry as that of 1.

Dolastatin H and Isodolastatin H, Potent Cytotoxic Peptides from the Sea Hare Dolabella auricularia: Isolation, Stereostructures, and Synthesis

A bioassay-directed investigation of the cytotoxic constituents of the Japanese sea hare Dolabella auricularia resulted in the isolation of two cytotoxic compounds designated dolastatin H (2) and i...

Dolabelides A and B, cytotoxic 22-membered macrolides isolated from the sea hare Dolabella auricularia

A new 22-membered macrolides, dolabelide A ( 1), and its deacetyl derivative, dolabelide B ( 2), have been isolated as cytotoxins from the Japanese sea hare Dolabella auricularia. The gross structures of 1 and 2 were determined by spectroscopic analysis, and their absolute stereochemistry was elucidated by a combination of chemical means and the NMR spectroscopic method.

Dolastatin E, a New Cyclic Hexapeptide Isolated from the Sea Hare Dolabella auricularia

Dolastatin E (1), a new cyclic hexapeptide containing three kinds of five-membered heterocycles (oxazole, thiazole, and thiazolone), has been isolated from the Japanese sea hare Dolabella auricularia and its gross structure elucidated by spectroscopic analysis.

Dolastatin E, a new cyclic hexapeptide isolated from the sea hare Dolabella auricularia

Dolastatin E ( 1), a new cyclic hexapeptide containing three kinds of five-membered heterocycles (oxazole, thiazole, and thiazolone), has been isolated from the Japanese sea hare Dolabella auricularia and its gross structure elucidated by spectroscopic analysis.