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

来自海绵 Theonella swinhoei 的高细胞毒性多肽 Theostatins A-C 的结构和活性。

基本信息

批准号：
05454096
负责人：
FUSETANI Nobuhiro
金额：
$ 4.42万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

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.

通过氨基酸分析和酸水解物的NMR数据鉴定出高度细胞毒性多肽A-C，已从海绵swinhoei中分离出来。它们的序列是通过解释2D NMR日期来确定的。 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.有趣的是，该序列是严格交替的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在氯仿和甲醇的1：1混合物中测量的NMR和CD光谱表明多理性胺B在该溶剂中采用了某些二级结构。根据2D NMR分析获得的约束，该溶剂中构象的DADAS90计算表明，它形成了右手的β-螺旋。这类似于毛孔形成肽的报道，gramicidin A.因此，聚理解酰胺B可能与脂质bilayr一样形成毛孔。