The hoiamides, structurally intriguing neurotoxic lipopeptides from Papua New Guinea marine cyanobacteria.
Two related peptide metabolites, one a cyclic depsipeptide, hoiamide B (2), and the other a linear lipopeptide, hoiamide C (3), were isolated from two different collections of marine cyanobacteria obtained in Papua New Guinea. Their structures were elucidated by combining various techniques in spectroscopy, chromatography, and synthetic chemistry. Both metabolites belong to the unique hoiamide structural class, characterized by possessing an acetate extended and S-adenosyl methionine modified isoleucine unit, a central triheterocyclic system comprised of two alpha-methylated thiazolines and one thiazole, and a highly oxygenated and methylated C-15 polyketide unit. In neocortical neurons, the cyclic depsipeptide 2 stimulated sodium influx and suppressed spontaneous Ca(2+) oscillations with EC(50) values of 3.9 microM and 79.8 nM, respectively, while 3 had no significant effects in these assays.
Choi
Hyukjae
H
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, USA.
Pereira
Alban R
AR
Cao
Zhengyu
Z
Shuman
Cynthia F
CF
Engene
Niclas
N
Byrum
Tara
T
Matainaho
Teatulohi
T
Murray
Thomas F
TF
Mangoni
Alfonso
A
Gerwick
William H
WH
D000818:Animals; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005260:Female; D006801:Humans; D055666:Lipopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008386:Marine Biology; D051379:Mice; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010219:Papua New Guinea; D011247:Pregnancy
D047630:Depsipeptides; D055666:Lipopeptides; D009498:Neurotoxins; C545734:hoiamide A; C552143:hoiamide B; C552144:hoiamide C