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Papuamides A-D, HIV-inhibitory and cytotoxic depsipeptides from the sponges Theonella mirabilis and Theonella swinhoei collected in Papua New Guinea

TitlePapuamides A-D, HIV-inhibitory and cytotoxic depsipeptides from the sponges Theonella mirabilis and Theonella swinhoei collected in Papua New Guinea
Publication TypeJournal Article
Year of Publication1999
AuthorsFord, PW, Gustafson, KR, McKee, TC, Shigematsu, N, Maurizi, LK, Pannell, LK, Williams, DE, De Silva, ED, Lassota, P, Allen, TM, Van Soest, R, Andersen, RJ, Boyd, MR
JournalJournal of the American Chemical Society
Volume121
Pagination5899-5909
Date PublishedJun
Type of ArticleArticle
ISBN Number0002-7863
KeywordsACIDS, ANTIFUNGAL CYCLIC-PEPTIDES, CALLIPELTA, CYCLOTHEONAMIDES, ENANTIOMERICALLY PURE, GLYCOPEPTIDE, inhibitors, MARINE NATURAL-PRODUCTS, MOZAMBIQUE, POTENT THROMBIN INHIBITORS, SERINE-PROTEASE, SP
Abstract

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.

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