1994 Fiscal Year Final Research Report Summary
The structure and activities of theostatins A-C,highly cytotoxic polypeptides from the marine sponge Theonella swinhoei.
| Project/Area Number |
05454096
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Fisheries chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
FUSETANI Nobuhiro The University of Tokyo.Faculty of Agriculture.Professor., 農学部, 教授 (70012010)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUNAGA Shigeki The university of Tokyo.Faculty of Agriculture.Assistant Professor., 農学部, 助手 (60183951)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Cytotoxic / Polypeptides / Marine sponge / Unusual amino acids / Absolute configuration / Conformation / beta-helix / Pore-forming |
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| Research Abstract |
Highly cytotoxic polypeptides, polytheonamides A-C,have been isolated from the marine sponge Theonella swinhoei.
The component amino acids of polytheonamides A-C were identified by amino acid analysis and NMR data of the acid hydrolysates. Their sequences were determined by interpretation of 2D NMR date. Polytheonamides are 48-residue polypeptides with N-terminus blocked by a carbamoyl group, and contain unusual amino acids such as t-Leu, betaMeIle, betaOHVal, betaOHAsm, betaMeGln, and OH-t-Leu.
The absolute configuration of each amino acid residue in polytheonamide B were determined by chiral chromatographies of the partial acid hydrolysates. Interestingly, the sequence is a strictly alternating DL.
NH_2CO-Gly-L-betaMeIle -Gly-L -t-Leu-D-t-Leu-L-t-Leu-D-Ala-L-t-Leu-D-t-Leu-L-Ala-Gly-L-Ala-D-t-Leu-L-Ala-D-Asm-betaOHVal-Gly-L-Ala-Gly-L-t-Leu-D-Asm-betaMeGln-betaOHVal-L-Ala-Gly-Gly-D-Asm-L-Ile-D-betaOHAsm-L-t-Leu-D-betaOHVal-Gly-D-Asm-L-Ile-D-Asm-L-Val-D-betaOHAsm-L-Ala-D-Asm-L-Val-D-Ser-L-Val-D-Asn-OH-t-Leu-D-Asn-L-Gln-L-Thr-D-aThr
The NMR and CD spectra measured in a 1 : 1 mixture of chloroform and methanol indicated that polytheonamide B adopted certain secondary structure in this solvent. The DADAS90 calculations of the conformation in this solvent based on the constraints obtained by 2D NMR analyzes revealed that it formed a right-handed beta-helix. This is similar to that reported for the pore-forming peptide, gramicidin A.Therefore, polytheonamide B likely forms a pore in lipid bilayr as does gramicidin A.
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