Papuamides A-D, HIV-inhibitory and cytotoxic depsipeptides from the sponges Theonella mirabilis and Theonella swinhoei collected in Papua New Guinea
Papuamides A-D, HIV-inhibitory and cytotoxic depsipeptides from the sponges Theonella mirabilis and Theonella swinhoei collected in Papua New Guinea
复制标题
DOI：
10.1021/ja990582o
复制
发表时间：
1999-06-30
影响因子：
15
通讯作者：
Boyd, MR
中科院分区：
文献类型：
--
作者：
Ford, PW;Gustafson, KR;Boyd, MR
新型环状沉积肽papuamides A (1), B (2)， C(3)和D(4)从巴布亚新几内亚的海绵Theonella mirabilis和Theonella swinhoei中分离得到。通过光谱分析、化学降解和衍生化研究确定了它们的结构。除了甘氨酸、丙氨酸和苏氨酸外，这些肽还含有许多不寻常的氨基酸，包括3,4-二甲基谷氨酰胺、β -甲氧基酪氨酸、3-甲氧基丙氨酸和2,3-二氨基丁酸或2-氨基-2-丁酸残基。Papuamides A-D（1-4）也是报道的第一个含有3-羟基亮氨酸和同脯氨酸残基的海洋衍生肽。这些肽还含有先前描述过的2,3-二羟基-2,6,8-三甲基十a-(4Z,6E)-二烯酸部分n -与末端甘氨酸残基相连。木瓜酰胺A(1)和B(2)在体外抑制HIV-1（RF）对人t淋巴母细胞样细胞的感染，EC50约为4 ng/mL。化合物1也对一组人类癌细胞具有细胞毒性，平均IC50为75 ng/mL。
The novel cyclic depsipeptides papuamides A (1), B (2), C (3), and D (4) have been isolated from Papua New Guinea collections of the sponges Theonella mirabilis and Theonella swinhoei. Their structures were determined by a combination of spectroscopic analysis and chemical degradation and derivatization studies. In addition to glycine, alanine, and threonine, these peptides contain a number of unusual amino acids including 3,4-dimethylglutamine, beta-methoxytyrosine, 3-methoxyalanine, and 2,3-diaminobutanoic acid or 2-amino-2-butenoic acid residues. Papuamides A-D (1-4) are also the first marine-derived peptides reported to contain 3-hydroxyleucine and homoproline residues. These peptides also contain a previously undescribed 2,3-dihydroxy-2,6,8-trimethyldeca-(4Z,6E)-dienoic acid moiety N-linked to a terminal glycine residue. Papuamides A (1) and B (2) inhibited the infection of human T-lymphoblastoid cells by HIV-1(RF) in vitro with an EC50 of approximately 4 ng/mL. Compound 1 was also cytotoxic against a panel of human cancer cell lines with a mean IC50 of 75 ng/mL.