8-O-Methylsclerotiorinamine, antagonist of the Grb2-SH2 domain, isolated from Penicillium multicolor.
A new secondary metabolite, 8-O-methylsclerotiorinamine (1), was isolated from a strain of Penicillium multicolor, and its structure was established using NMR spectroscopy and chemical evidence. The metabolite inhibited significantly the binding between the Grb2-SH2 domain and the phosphopeptide derived from the Shc protein and also blocked the protein-protein interactions of Grb2-Shc in cell-based experiments, with IC(50) values of 5.3 and 50 microM, respectively.
Nam
J Y
JY
Korea Research Institute of Bioscience & Biotechnology, 52 Uen-dong, Yusung, Taejon, 305-333, Republic of Korea.
Kim
H K
HK
Kwon
J Y
JY
Han
M Y
MY
Son
K H
KH
Lee
U C
UC
Choi
J D
JD
Kwon
B M
BM
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; D007546:Isoquinolines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015394:Molecular Structure; D010407:Penicillium / Q000737:chemistry*; D011485:Protein Binding; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013057:Spectrum Analysis; D018909:src Homology Domains / Q000187:drug effects*
C417934:8-O-methylsclerotiorinamine; D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; D007546:Isoquinolines; D011506:Proteins