Design and synthesis of an artificial ladder-shaped polyether that interacts with glycophorin A.
Ladder-shaped polyether (LSP) compounds, such as brevetoxins and ciguatoxins, are thought to interact with transmembrane (TM) proteins. As a model LSP compound, we designed and synthesized an artificial tetracyclic ether (1) and evaluated its interaction with glycophorin A (GpA), a membrane protein known to dimerize or oligomerize between membrane-integral alpha-helical domains. Model compound 1 was found to induce the dissociation of oligomeric GpA in a similar manner to natural LSPs when examined by SDS-PAGE. The results suggest that even an artificial tetracyclic ether possesses the ability to interact with TM proteins, presumably through the intermolecular hydrogen bonds (C(alpha)-Hcdots, three dots, centeredO) with the GXXXG motif.
Torikai
Kohei
K
Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.
Yari
Hiroshi
H
Mori
Megumi
M
Ujihara
Satoru
S
Matsumori
Nobuaki
N
Murata
Michio
M
Oishi
Tohru
T
D002922:Ciguatoxins / Q000737:chemistry*; D004987:Ethers / Q000737:chemistry; D004988:Ethers, Cyclic / Q000737:chemistry; D006021:Glycophorins / Q000737:chemistry*; D008387:Marine Toxins / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D008978:Mollusk Venoms; D035964:Oxocins / Q000737:chemistry*; D000095702:Polyether Toxins
D002922:Ciguatoxins; D004987:Ethers; D004988:Ethers, Cyclic; D006021:Glycophorins; D008387:Marine Toxins; D008978:Mollusk Venoms; D035964:Oxocins; C458159:gymnocin A; C043466:brevetoxin B; D000095702:Polyether Toxins; C066632:yessotoxin