Abstract
A novel protein, soritesidine (SOR) with potent toxicity was isolated from the marine sponge Spongosorites sp. SOR exhibited wide range of toxicities over various organisms and cells including brine shrimp (Artemia salina) larvae, sea hare (Aplysia kurodai) eggs, mice, and cultured mammalian cells. Toxicities of SOR were extraordinary potent. It killed mice at 5 ng/mouse after intracerebroventricular (i.c.v.) injection, and brine shrimp and at 0.34 µg/mL. Cytotoxicity for cultured mammalian cancer cell lines against HeLa and L1210 cells were determined to be 0.062 and 12.11 ng/mL, respectively. The SOR-containing fraction cleaved plasmid DNA in a metal ion dependent manner showing genotoxicity of SOR. Purified SOR exhibited molecular weight of 108.7 kDa in MALDI-TOF MS data and isoelectric point of approximately 4.5. N-terminal amino acid sequence up to the 25th residue was determined by Edman degradation. Internal amino acid sequences for fifteen peptides isolated from the enzyme digest of SOR were also determined. None of those amino acid sequences showed similarity to existing proteins, suggesting that SOR is a new proteinous toxin.
Highlights
Marine sponges are known to be rich sources of novel bioactive peptides [1,2]
An aqueous extract of sponge specimen collected in Iriomote, Okinawa and identified to be Spongosorites sp. showed conspicuously potent cytotoxicity against three cancer cell lines and brine shrimp larvae
Is a previously uncharacterizedprotein protein.sequences did not result in significant match with the E-value of less than 0.001. These results indicated that SOR is a previously uncharacterized protein
Summary
Marine sponges are known to be rich sources of novel bioactive peptides [1,2] They are mostly small cyclic molecules (molecular weight, MW < 2000) composed of non-proteinous amino acids or even non-amino acid components, and are thought to be of non-ribosomal origin. There are, several examples of middle sized (MW < 6000) ribosomal peptides including polytheonamides [3], asteropines and related molecules [4,5], and aculeines [6] are known. The unique modifications may add extra stability and structural characteristics to the molecules which in turn lead to specific and potent biological activities of the molecules. Besides these relatively small peptides, sponges are known to contain large ‘bioactive’
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