Complestatin, a potent anti-complement substance produced by Streptomyces lavendulae. I. Fermentation, isolation and biological characterization.
A new potent inhibitor of complement system, named complestatin, was isolated from the mycelium of Streptomyces lavendulae SANK 60477. Complestatin (C61H45N7O15Cl6, MW 1,325) was a peptide compound having two unusual amino acids, D-(-)-4-hydroxyphenylglycine and D-(-)-3,5-dichloro-4-hydroxyphenylglycine. This compound inhibited the hemolysis of sensitized sheep erythrocytes (EA) mediated by guinea pig and human complement 50% at concentrations of 0.4 and 0.7 micrograms/ml, respectively, but did not trypsin and alpha-chymotrypsin activities at 200 micrograms/ml. When complestatin was administered intravenously to the sensitized guinea pigs, it strongly inhibited the systemic anaphylactic shock elicited by the antigen probably by blocking generation of anaphylatoxins (C3a and C5a).
Kaneko
I
I
Institute of Science and Technology, Sankyo Co., Ltd., Tokyo, Japan.
Kamoshida
K
K
Takahashi
S
S
D000596:Amino Acids / Q000302:isolation & purification / Q000494:pharmacology; D000707:Anaphylaxis / Q000517:prevention & control; D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification*; D002733:Chlorophenols; D002918:Chymotrypsin / Q000378:metabolism; D003167:Complement Activation / Q000187:drug effects; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D005285:Fermentation; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects; D010456:Peptides, Cyclic; D013302:Streptomyces / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D002733:Chlorophenols; D003169:Complement Inactivator Proteins; D010456:Peptides, Cyclic; C023490:complestatin; D002918:Chymotrypsin; D014357:Trypsin