Sanglifehrins A, B, C and D, novel cyclophilin-binding compounds isolated from Streptomyces sp. A92-308110. I. Taxonomy, fermentation, isolation and biological activity.
A novel class of macrolides for which the name sanglifehrins is proposed, has been discovered from actinomycete strains based on their high affinity binding for cyclophilin A (CypA), an immunophilin originally identified as a cytosolic protein binding cyclosporin A (CsA). The sanglifehrins were produced by Streptomyces sp. A92-308110. They were isolated and purified by extraction and several chromatographic, activity-guided steps. Sanglifehrins A and B exhibit a 10 to approximately 20 fold higher affinity for CypA than CsA, whereas the affinity of sanglifehrins C and D for CypA is comparable to that of CsA. Sanglifehrins exhibit a lower immunosuppressive activity than CsA when tested in the mixed lymphocyte reaction. Their in vitro activity indicates that they belong to a novel class of immunosuppressants.
Sanglier
J J
JJ
Novartis Pharma Inc., Research, Departments of Core Technology and Transplantation, Basel, Switzerland.
Quesniaux
V
V
Fehr
T
T
Hofmann
H
H
Mahnke
M
M
Memmert
K
K
Schuler
W
W
Zenke
G
G
Gschwind
L
L
Maurer
C
C
Schilling
W
W
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D016572:Cyclosporine / Q000378:metabolism; D020104:Immunophilins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D018942:Macrolides; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D013141:Spiro Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D013302:Streptomyces / Q000145:classification / Q000254:growth & development / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D007783:Lactones; D018942:Macrolides; D013141:Spiro Compounds; C121329:sanglifehrin A; C121333:sanglifehrin B; C121331:sanglifehrin C; C121332:sanglifehrin D; D016572:Cyclosporine; D020104:Immunophilins