Sanglifehrins A, B, C and D, Novel Cyclophilin-binding Compounds Isolated from Streptomyces sp. A92-308110 I. Taxonomy, Fermentation, Isolation and Biological Activity

JEAN-JACQUES SANGLIER; VALERIE QUESNIAUX; THEODOR FEHR; HANS HOFMANN; MARION MAHNKE; KLAUS MEMMERT; WALTER SCHULER; GERHARD ZENKE; LILIANE GSCHWIND; CLAUDINE MAURER; WOLFGANG SCHILLING

doi:10.7164/antibiotics.52.466

Sanglifehrins A, B, C and D, Novel Cyclophilin-binding Compounds Isolated from Streptomyces sp. A92-308110

I. Taxonomy, Fermentation, Isolation and Biological Activity

JEAN-JACQUES SANGLIER, VALERIE QUESNIAUX, THEODOR FEHR, HANS HOFMANN, MARION MAHNKE, KLAUS MEMMERT, WALTER SCHULER, GERHARD ZENKE, LILIANE GSCHWIND, CLAUDINE MAURER, WOLFGANG SCHILLING

Author information

JEAN-JACQUES SANGLIER
Novartis Pharma Inc., Research, Departments of Core Technology and Transplantation
VALERIE QUESNIAUX
Novartis Pharma Inc., Research, Departments of Core Technology and Transplantation
THEODOR FEHR
Novartis Pharma Inc., Research, Departments of Core Technology and Transplantation
HANS HOFMANN
Novartis Pharma Inc., Research, Departments of Core Technology and Transplantation
MARION MAHNKE
Novartis Pharma Inc., Research, Departments of Core Technology and Transplantation
KLAUS MEMMERT
Novartis Pharma Inc., Research, Departments of Core Technology and Transplantation
WALTER SCHULER
Novartis Pharma Inc., Research, Departments of Core Technology and Transplantation
GERHARD ZENKE
Novartis Pharma Inc., Research, Departments of Core Technology and Transplantation
LILIANE GSCHWIND
Novartis Pharma Inc., Research, Departments of Core Technology and Transplantation
CLAUDINE MAURER
Novartis Pharma Inc., Research, Departments of Core Technology and Transplantation
WOLFGANG SCHILLING
Novartis Pharma Inc., Research, Departments of Core Technology and Transplantation

JOURNAL FREE ACCESS

1999 Volume 52 Issue 5 Pages 466-473

DOI https://doi.org/10.7164/antibiotics.52.466

Details

Abstract

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 10-20 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.

Corresponding author

Register with J-STAGE for free!