Isolation and characterization of a novel protein toxin from the Hawaiian box jellyfish (sea wasp) Carybdea alata.

The box jellyfish (sea wasp) Carybdea alata Reynaud, 1830 (Cubozoa) is distributed widely in the tropics. The sting of C. alata causes severe pain and cutaneous inflammation in humans. We successfully isolated C. alata toxin-A (CaTX-A, 43 kDa) and -B (CaTX-B, 45 kDa) for the first time from the tentacle of C. alata collected at a site along the Hawaiian shore. The experimental results showed that CaTX-A, but not CaTX-B, is present in the nematocyst, the organ responsible for stinging. Both CaTX-A and -B showed potent hemolytic activity, with CaTX-A being lethally toxic to crayfish when administered via intraperitoneal injection. Furthermore, we sequenced the cDNA encoding CaTX-A. The deduced amino acid sequence of CaTX-A (463 amino acids) showed 43.7% homology to Carybdea rastoni toxins (CrTXs) but not with any other known proteins. Therefore, these jellyfish toxins potentially represent a novel class of bioactive proteins. Secondary structure analysis of CaTX-A and CrTXs suggested the presence of amphiphilic alpha-helices, which are also seen in several known hemolytic or cytolytic protein toxins, including peptide toxins.

New triterpenoid sulfates from the red alga Tricleocarpa fragilis.

Ten new sulfated terpenoids, including six cycloartenol sulfates (1-6), two 29-nor-cycloartenol sulfates (7,8), and two 29-nor-lanosterol sulfates (9,10), were isolated from brine shrimp-toxic fractions of the methanolic extract of the red alga Tricleocarpa fragilis collected in Hawaiian waters. Structures 1-10 were elucidated by spectral methods, and the absolute stereochemistry for compound 1 at C23 was determined by Mosher analysis. Compounds 7 and 10 showed brine shrimp toxicity at 50 microg/mL, while 1 and 3 showed substantial activity at 17 microg/mL. Compounds 2, 4, 5, and 9 were inactive. In cytotoxicity assays, compounds 1-10 were inactive at concentrations tested.

A new depsipeptide from the sacoglossan mollusk Elysia ornata and the green alga Bryopsis species.

A new cyclic depsipeptide, kahalalide O (1), was isolated from the sacoglossan Elysia ornata and its algal diet Bryopsis sp. The structure was elucidated primarily by NMR and MS spectral methods, and the stereochemistry of the amino acid residues was determined by chiral HPLC and Marfey analyses. Unlike the related metabolite kahalalide F, which is in development as a potential anticancer agent, kahalalide O (1) was inactive in arresting the growth of P-388, A549, HT29, and MEL28 cancer cell lines in vitro.

New malyngamides from the Hawaiian cyanobacterium Lyngbya majuscula.

Isomalyngamides A and B (1, 2) were isolated and characterized from a collection of the cyanobacterium Lyngbya majuscula from Hawaiian waters. These compounds represent a new type of malyngamide, similar to malyngamides Q and R, in which the conformation of the chloromethylene group is opposite from the majority of previously reported malyngamides. The geometry of the chloromethylene moiety was elucidated from the long-range coupling constants ((3)J(C)(-)(H)) obtained from editing-HETLOC and phase-sensitive HMBC experiments. Isomalyngamides A and B (1, 2) showed lethal toxicity to crayfish.

Kahalalide K: A new cyclic depsipeptide from the hawaiian green alga bryopsis species

Kahalalide K (1), a new cyclic depsipeptide, was isolated from the Hawaiian green alga Bryopsis sp. Kahalalide K was determined to possess a new array of three L- and three D-amino acids, including a 3-hydroxy-9-methyldecanoic acid that had been previously reported in kahalalides E, H, and J.

Malyngamides M and N from the Hawaiian Red Alga Gracilaria coronopifolia

Two new malyngamides, M and N (1, 2), were isolated along with malyngamide I acetate (3) from the Hawaiian red alga Gracilaria coronopifolia. Our results suggest that malyngamide N (2) is a revised structure of deacetoxystylocheilamide (5). The absolute configuration of malyngamide I acetate was deduced to be 3 using the reversed octant rule.

Manauealide C and Anhydrodebromoaplysiatoxin, Toxic Constituents of the Hawaiian Red Alga, Gracilaria coronopifolia.

Manauealide C (1) and anhydrodebromoaplysiatoxin (4), toxic constituents of the Hawaiian red alga, Gracilaria coronopifolia which has been concerned with food poisoning cases, were studied. The absolute structure of manauealide C was determined as 1 by chemical conversion and spectroscopic methods. The first complete assignment of (13)C chemical shifts for anhydrodebromoaplysiatoxin (4) was established. The biological activity of 4 was also investigated.

Antagonism between retinoic acid receptors and AP-1: implications for tumor promotion and inflammation.

Retinoids such as retinoic acid (RA) are potent anti-arthritic and anti-neoplastic agents. We investigated the mechanism by which RA inhibits induction of collagenase gene transcription by inflammatory mediators, tumor promoters, and proto-oncogenes. We found that the RA receptors (RARs) are potent inhibitors of AP-1 activity generated either by cJun homodimers or cJun/cFos heterodimers. In addition, both cJun and cFos can inhibit RAR activity. In vitro experiments suggested that this inhibition is due to an interaction between RAR and AP-1 proteins that results in mutual loss of DNA-binding activity. The RARs need not bind to the AP-1 site, neither does AP-1 bind to RA response elements. An understanding of this antagonism between the RAR and AP-1 might help to elucidate the anti-neoplastic and anti-arthritic effects of RA as well as its effects on cell differentiation and proliferation.