Isolation and structural elucidation of cyclic tetrapeptides from Onychocola sclerotica.
Three new cyclic tetrapeptides (1-3) have been isolated from the crude fermentation extract of Onychocola sclerotica. The planar structures of 1-3 were elucidated by detailed spectroscopic analyses using one- and two-dimensional NMR experiments and high-resolution mass spectrometry. The absolute configuration of the amino acid residues in each cyclotetrapeptide was established by Marfey's method. Compounds 1-3 displayed activity as cardiac calcium channel blockers (Cav1.2) but did not inhibit the hERG potassium channel and were not cytotoxic. These peptides are the first secondary metabolites ever reported from fungi of the order Arachnomycetales.
Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Avenida del Conocimiento 3, Parque Tecnológico de Ciencias de la Salud, E-18100 Armilla, Granada, Spain. ignacio.perez-victoria@medinaandalucia.es
Ignacio
I
Pérez-Victoria
Jesús
J
Martín
Víctor
V
González-Menéndez
Nuria
N
de Pedro
Noureddine
N
El Aouad
Francisco Javier
FJ
Ortiz-López
José Rubén
JR
Tormo
Gonzalo
G
Platas
Francisca
F
Vicente
Gerald F
GF
Bills
Olga
O
Genilloud
Michael A
MA
Goetz
Fernando
F
Reyes
D000596:Amino Acids; D001203:Ascomycota / Q000737:chemistry*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects; D005285:Fermentation; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014665:Vasodilator Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D000596:Amino Acids; D020746:Calcium Channels, L-Type; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C419385:L-type calcium channel alpha(1C); D010456:Peptides, Cyclic; D014665:Vasodilator Agents; C574911:cyclo-(N-MePhe-Ile)2; C574912:cyclo-(N-MePhe-Val)2; C574910:cyclo-(N-MePhe-Val-N-MePhe-Ile)