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

Abstract

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 Nδ-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.

Use of Marfey's reagent and analogs for chiral amino acid analysis: Assessment and applications to natural products and biological systems

“…From deep-water specimen of T. swinhoei and Theonella cupola sulfated cyclic depsipeptide, termed mutremdamide A, and six highly N-methylated peptides, termed koshikamides C-H, were isolated and the structure of unusual AAs was determined using advanced Marfey's method and chiral HPLC together with intensive use of NMR and mass spectrometric methods [84].…”

Configurational assignments of conformationally restricted bis-monoterpene hydroquinones: Utility in exploration of endangered plants

“…3). The total absolute deviation (TAD) [12,13] between the experimental and calculated values (Table 2, Fig. 3) suggested that the calculated SSCCs of diastereomer I in Fig.…”

“…The SSCC of each rotamer was calculated using the same theory and basis set in Gaussian09 [11]. The total absolute deviation (TAD) [12,13] between experimental and calculated values was used to suggest the most relevant conformers, and by extension of the empirical results, their configuration.…”

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“…Celebeside A neutralized HIV-1 in a single-round infectivity assay with an IC50 value of 1.9±0.4μg/mL while the nonphosphorylated analog celebeside C was inactive at concentrations as high as 50 μg/mL 69 . HIV cyclodepsipeptide, homophymine A, was isolated from a New Caledonian collection of the marine sponge Homophymia sp.…”

“…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 69 . The origin and role of bioactive peptides inside the sponges in many cases is unclear.Several of these substances possess a great potential for drug development, but none has given origin to a commercial medication so far.…”