The structure and activities of theostatins A-C,highly cytotoxic polypeptides from the marine sponge Theonella swinhoei.

从海绵海绵中分离到具有高细胞毒性的多肽，即聚酰胺A-C。通过氨基酸分析和核磁共振数据对聚胺A-C的组成氨基酸进行了鉴定。它们的序列由二维核磁共振数据解释确定。聚酰胺是一种含有48个残基的多肽，其n端被氨基基阻断，含有不常见的氨基酸，如t-Leu、betaMeIle、betaOHVal、betaOHAsm、betaMeGln和OH-t-Leu。用部分酸水解物的手性色谱法测定了聚乙酰胺中各氨基酸残基的绝对构型。有趣的是，这个序列是一个严格交替的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-aThrThe NMR和CD光谱测量在1:1氯仿和甲醇的混合物表明polytheonamide B采用某些二级结构在这种溶剂。基于二维核磁共振分析得到的约束条件，DADAS90计算了该溶剂中的构象，结果表明它形成了右手型β -螺旋。这与报道的成孔肽gramicidin a相似。因此，聚茶酰胺B可能在脂质双层中形成孔，gramicidin a也是如此。

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-aThrThe 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.