Mutremdamide A and koshikamides C-H, peptide inhibitors of HIV-1 entry from different Theonella species.
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(delta)-carbamoyl-beta-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.
Plaza
Alberto
A
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Bifulco
Giuseppe
G
Masullo
Milena
M
Lloyd
John R
JR
Keffer
Jessica L
JL
Colin
Patrick L
PL
Hooper
John N A
JN
Bell
Lori J
LJ
Bewley
Carole A
CA
D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D047630:Depsipeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008387:Marine Toxins / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D047232:Theonella / Q000737:chemistry*
D047630:Depsipeptides; D008387:Marine Toxins; D010456:Peptides, Cyclic; C553195:koshikamide F; C553188:mutremdamide A
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