Total synthesis and evaluation of Wnt signal inhibition of melleumin A and B, and their derivatives.
The total synthesis of melleumin A (1), a novel cyclic depsipeptide isolated from the myxomycete Physarum melleum, and 3-epi-melleumin A (6) was achieved. Melleumin A-like compounds were also designed and synthesized; analysis of these melleumin A-like compounds showed moderate Wnt signal inhibition. Comparison of the inhibition activity of melleumin B and its three epimers, melleumin A, 3-epi-melleumin A and three melleumin A-like compounds led to further investigation of the structural conformation of the active molecules. The scaffold of melleumin is a potential target in the search for "peptide-like" Wnt signaling inhibitors.
Arai
Midori A
MA
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan. marai@p.chiba-u.ac.jp
Hanazawa
Shuwa
S
Uchino
Yujiro
Y
Li
Xiaofan
X
Ishibashi
Masami
M
D018360:Crystallography, X-Ray; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D015398:Signal Transduction / Q000187:drug effects*; D051153:Wnt Proteins / Q000378:metabolism
D047630:Depsipeptides; D051153:Wnt Proteins; C539389:melleumin A; C539390:melleumin B