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。

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454096/
• 关键词: Cytotoxic; Polypeptides; Marine sponge; Unusual amino acids; Absolute configuration; Conformation; beta-helix; Pore-forming; 二次元NMR; 立体; Theonella swinhoei; ペプチド; アミノ酸分析; 2次元NMR; FAB-MS

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.

从海绵Theonella swinhoei中分离得到一种具有高细胞毒性的多肽--聚茶酰胺（polytheonamides）A-C，通过氨基酸分析和酸水解产物的核磁共振谱（NMR）数据鉴定了其组成氨基酸。通过2DNMR数据的解释确定了它们的序列。Polytheonamide是一种N-端被氨基甲酰基封闭的48个氨基酸残基的多肽，含有t-Leu、betaMeIle、betaOHVal、betaOHAsm、betaMeGln和OH-t-Leu等不常见的氨基酸。有趣的是，其序列为严格交替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-bebe taOH瓦尔-Gly-L-Ala-Gly-L-t-Leu-D-Asm-betaMeGln-betaOH瓦尔-L-Ala-Gly-Gly-D-Gly @ m-L-Ile-D-betaOHAsm-L-t-Leu-D-betaOH瓦尔-Gly-D-Asm-L-Ile-D-Asm-L-瓦尔-D-甜菜碱@ OHAsm-L-Ala-D-Asm-L-瓦尔-D-Ser-L-瓦尔-D-Asn-OH-t-Leu-D-Asn-L-Gln-L-Thr-D-aThr在1：1的氯仿-甲醇混合溶剂中的NMR和CD谱表明聚茶酰胺B在该溶剂中具有一定的二级结构。基于通过2D NMR分析获得的约束，在该溶剂中构象的DADAS 90计算显示其形成右手β-螺旋。这与所报道的成孔肽短杆菌肽A相似。因此，聚茶酰胺B可能与短杆菌肽A一样在脂质双层中形成孔。

项目成果

Toshiyuki Hamada et al.: "Polytheonamides A-C,highly cytotoxic polypeptides from the marine sponge Theonella swinhoei" Sponges in Time and Space, Balkema. 453-457 (1994)

Toshiyuki Hamada 等人：“Polytheonamides A-C，来自海洋海绵 Theonella swinhoei 的高细胞毒性多肽”《时空海绵》，巴尔克马。

Toshiyuki Hamada et al.: "Polytheonamides,Unprecedented Highly Cytotoxic Polypeptides,from the Marine Sponge Theonella swinhoei 1.Isolation and Component Amino Acids" Tetrahedron Letters. 35. 719-720 (1994)

Toshiyuki Hamada 等人：“聚神酰胺，前所未有的高细胞毒性多肽，来自海洋海绵 Theonella swinhoei 1. 氨基酸的分离和组成”四面体快报。

Toshiyuki Hamada et al.: "Polytheonamides A-C,highly cytotoxic polypeptides from the marine sponge Theonella swinhoei" Sponges in Time and Space,Balkema,Rotterdam. 453-457 (1994)

Toshiyuki Hamada 等人：“Polytheonamides A-C，来自海洋海绵 Theonella swinhoei 的高细胞毒性多肽”《时空海绵》，Balkema，鹿特丹。

Toshiyuki Hamada,et al.: "Polytheonamides,Unprecedented Highly Cytotoxic Polypeptides,from the Marine Sponge Theonella swinhoei 1.Isolation and Component Amino Acids" Tetrahedron Letters. 35. 719-720 (1994)

Toshiyuki Hamada 等人：“聚神酰胺，前所未有的高细胞毒性多肽，来自海洋海绵 Theonella swinhoei 1. 氨基酸的分离和组成”四面体字母。

Nobuhiro Fusetani: "Polytheonamides A-C,highly cytotoxic polypeptides from the marine sponge Theonella swinhoei" Proc.Int.4th Porifera Congress. (印刷中).

Nobuhiro Fusetani：“Polytheonamides A-C，来自海洋海绵 Theonella swinhoei 的高细胞毒性多肽”Proc.Int.第四届 Porifera 大会（正在出版）。