Mutremdamide A and Koshikamides C−H, Peptide Inhibitors of HIV-1 Entry from Different Theonella Species

• Published in: Journal of organic chemistry Vol. 75; no. 13; pp. 4344 - 4355
• Main Authors: Plaza, Alberto, Bifulco, Giuseppe, Masullo, Milena, Lloyd, John R, Keffer, Jessica L, Colin, Patrick L, Hooper, John N. A, Bell, Lori J, Bewley, Carole A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 02-07-2010
• Subjects: Animals; Cell Line, Tumor - drug effects; Chromatography, High Pressure Liquid; Depsipeptides - chemistry; Depsipeptides - isolation & purification; Depsipeptides - pharmacology; HIV-1 - drug effects; Humans; Marine Toxins - chemistry; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Peptides, Cyclic - chemistry; Peptides, Cyclic - isolation & purification; Peptides, Cyclic - pharmacology; Theonella - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo100076g

A new sulfated cyclic depsipeptide, termed mutremdamide A, and six new highly N-methylated peptides, termed koshikamides C−H, were isolated from different deep-water specimens of Theonella swinhoei and Theonella cupola. Their structures were determined using extensive 2D NMR, ESI, or CDESI and QTOF-MS/MS experiments and absolute configurations established by quantum mechanical calculations, advanced Marfey’s method, and chiral HPLC. Mutremdamide A displays a rare 2-amino-3-(2-hydroxyphenyl)propanoic acid and a new N δ-carbamoyl-β-sulfated asparagine. Koshikamides C−E are linear undecapeptides, and koshikamides F−H are 17-residue depsipeptides containing a 10-residue macrolactone. Koshikamides F and G differ from B and H in part by the presence of the conjugated unit 2-(3-amino-5-oxopyrrolidin-2-ylidene)propanoic acid. Cyclic koshikamides F and H inhibited HIV-1 entry at low micromolar concentrations while their linear counterparts were inactive. The Theonella collections studied here are distinguished by co-occurrence of mutremdamide A, koshikamides, and theonellamides, the combination of which appears to define a new Theonella chemotype that can be found in deeper waters.