Isolation and structure determination of malevamide E, a dolastatin 14 analogue, from the marine cyanobacterium Symploca laete-viridis.
A new depsipeptide, malevamide E (1), was isolated from field-collected colonies of the filamentous cyanobacterium Symploca laete-viridis. The gross structure of 1 was determined by spectroscopic analyses, including one- and two-dimensional NMR and accurately measured MS/MS. Chiral HPLC analyses of an acid hydrolysate of 1 allowed the stereochemical assignments of its amino acid residues, which include N-methyl-L-alanine, alpha-N,gamma-N-dimethyl-L-asparagine, N-methyl-L-phenylalanine, L-proline, D-valine, and N-methyl-L-valine. LC-MS/MS analysis of S. laete-viridis fractions established the co-occurrence of malevamide E (1) and its homologue dolastatin 14 (2), which was previously reported in low yield from the sea hare Dolabella auricularia. Malevamide E (1) demonstrated a dose-dependent (2-45 microM) inhibition of store-operated Ca(2+) entry in thapsigargin-treated human embryonic kidney (HEK) cells, indicating an inhibitory effect on Ca(2+) release-activated Ca(2+) (CRAC) channels.
Adams
Beatrice
B
College of Natural Sciences, Hawaii Pacific University, Kaneohe, HI 96744, USA.
Pörzgen
Peter
P
Pittman
Emily
E
Yoshida
Wesley Y
WY
Westenburg
Hans E
HE
Horgen
F David
FD
D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D049851:Gastropoda / Q000737:chemistry*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D008386:Marine Biology; D015394:Molecular Structure; D019284:Thapsigargin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D047630:Depsipeptides; C530228:dolastatin 14; C530227:malevamide E; D019284:Thapsigargin