Asteropine A, a sialidase-inhibiting conotoxin-like peptide from the marine sponge Asteropus simplex.
Marine sponges contain structurally intriguing and biologically active peptides of nonribosomal peptide synthase origin, often containing amino acids with novel structures. Here we report the discovery of asteropine A (APA), a cystine knot to be isolated from marine sponges. The solution structure of APA as determined by NMR belongs to the four-loop class of cystine knots similar to those of some conotoxins and spider toxins. However, the highly negatively charged surface of APA is uncommon among other cystine knots. APA competitively inhibits bacterial sialidases, but not a viral sialidase. APA was inactive against all other enzymes tested and did not have any apparent antitumor activity. Our data suggest that APA and other knotting peptides may be important leads for antibacterial and even antiviral drug development.
Takada
Kentaro
K
Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
Hamada
Toshiyuki
T
Hirota
Hiroshi
H
Nakao
Yoichi
Y
Matsunaga
Shigeki
S
van Soest
Rob W M
RW
Fusetani
Nobuhiro
N
D000595:Amino Acid Sequence; D000818:Animals; D003016:Clostridium perfringens / Q000187:drug effects / Q000201:enzymology; D020916:Conotoxins / Q000737:chemistry* / Q000494:pharmacology; D017124:Conserved Sequence; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009792:Oceans and Seas; D011161:Porifera / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
D020916:Conotoxins; D004791:Enzyme Inhibitors; C512824:asteropine A, Asteropus simplex; D009439:Neuraminidase