Abstract
Hoiamide A, a novel bioactive cyclic depsipeptide, was isolated from an environmental assemblage of the marine cyanobacteria Lyngbya majuscula and Phormidium gracile collected in Papua New Guinea. This stereochemically complex metabolite possesses a highly unusual structure, which likely derives from a mixed peptide-polyketide biogenetic origin, and includes a peptidic section featuring an acetate extended and S-adenosyl methionine modified isoleucine moiety, a triheterocyclic fragment bearing two α-methylated thiazolines and one thiazole, and a highly oxygenated and methylated C15-polyketide substructure. Pure hoiamide A potently inhibited [3H]batrachotoxin binding to voltage-gated sodium channels (IC50 = 92.8 nM), activated sodium influx (EC50 = 2.31 μM) in mouse neocortical neurons, and exhibited modest cytotoxicity to cancer cells. Further investigation revealed that hoiamide A is a partial agonist of site 2 on the voltage-gated sodium channel.
| Original language | English |
|---|---|
| Pages (from-to) | 893-906 |
| Number of pages | 14 |
| Journal | Chemistry and Biology |
| Volume | 16 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 28 2009 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Drug Discovery
- Molecular Biology
- Clinical Biochemistry
- Molecular Medicine
- Pharmacology
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Hoiamide A, a Sodium Channel Activator of Unusual Architecture from a Consortium of Two Papua New Guinea Cyanobacteria. / Pereira, Alban; Cao, Zhengyu; Murray, Thomas F.; Gerwick, William H.
In: Chemistry and Biology, Vol. 16, No. 8, 28.08.2009, p. 893-906.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hoiamide A, a Sodium Channel Activator of Unusual Architecture from a Consortium of Two Papua New Guinea Cyanobacteria
AU - Pereira, Alban
AU - Cao, Zhengyu
AU - Murray, Thomas F.
AU - Gerwick, William H.
PY - 2009/8/28
Y1 - 2009/8/28
N2 - Hoiamide A, a novel bioactive cyclic depsipeptide, was isolated from an environmental assemblage of the marine cyanobacteria Lyngbya majuscula and Phormidium gracile collected in Papua New Guinea. This stereochemically complex metabolite possesses a highly unusual structure, which likely derives from a mixed peptide-polyketide biogenetic origin, and includes a peptidic section featuring an acetate extended and S-adenosyl methionine modified isoleucine moiety, a triheterocyclic fragment bearing two α-methylated thiazolines and one thiazole, and a highly oxygenated and methylated C15-polyketide substructure. Pure hoiamide A potently inhibited [3H]batrachotoxin binding to voltage-gated sodium channels (IC50 = 92.8 nM), activated sodium influx (EC50 = 2.31 μM) in mouse neocortical neurons, and exhibited modest cytotoxicity to cancer cells. Further investigation revealed that hoiamide A is a partial agonist of site 2 on the voltage-gated sodium channel.
AB - Hoiamide A, a novel bioactive cyclic depsipeptide, was isolated from an environmental assemblage of the marine cyanobacteria Lyngbya majuscula and Phormidium gracile collected in Papua New Guinea. This stereochemically complex metabolite possesses a highly unusual structure, which likely derives from a mixed peptide-polyketide biogenetic origin, and includes a peptidic section featuring an acetate extended and S-adenosyl methionine modified isoleucine moiety, a triheterocyclic fragment bearing two α-methylated thiazolines and one thiazole, and a highly oxygenated and methylated C15-polyketide substructure. Pure hoiamide A potently inhibited [3H]batrachotoxin binding to voltage-gated sodium channels (IC50 = 92.8 nM), activated sodium influx (EC50 = 2.31 μM) in mouse neocortical neurons, and exhibited modest cytotoxicity to cancer cells. Further investigation revealed that hoiamide A is a partial agonist of site 2 on the voltage-gated sodium channel.
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U2 - 10.1016/j.chembiol.2009.06.012
DO - 10.1016/j.chembiol.2009.06.012
M3 - Article
VL - 16
SP - 893
EP - 906
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 8
ER -