| Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1993: ¥5,700,000 (Direct Cost: ¥5,700,000)
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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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