Chemistry and biology of the immunophilins and their immunosuppressive ligands.

Cyclosporin A, FK506, and rapamycin are inhibitors of specific signal transduction pathways that lead to T lymphocyte activation. These immunosuppressive agents bind with high affinity to cytoplasmic receptors termed immunophilins (immunosuppressant binding proteins). Studies in this area have focused on the structural basis for the molecular recognition of immunosuppressants by immunophilins and the biological consequences of their interactions. Defining the biological roles of this emerging family of receptors and their ligands may illuminate the process of protein trafficking in cells and the mechanisms of signal transmission through the cytoplasm.

[1]  S. Burakoff,et al.  Probing immunosuppressant action with a nonnatural immunophilin ligand , 1990, Science.

[2]  F. Schmid,et al.  Isolation and sequence of an FK506-binding protein from N. crassa which catalyses protein folding , 1990, Nature.

[3]  Andrzej Galat,et al.  Molecular cloning and overexpression of the human FK506-binding protein FKBP , 1990, Nature.

[4]  G. Schulte,et al.  Discodermolide: a new bioactive polyhydroxylated lactone from the marine sponge Discodermia dissoluta , 1990 .

[5]  S. Schreiber,et al.  Substrate specificity for the human rotamase FKBP: a view of FK506 and rapamycin as leucine-(twisted amide)-proline mimics , 1990 .

[6]  M. Ptashne,et al.  Activators and targets , 1990, Nature.

[7]  S. Schreiber,et al.  Total synthesis of FK506 and an FKBP probe reagent, [C(8),C(9)-13C2]-FK506 , 1990 .

[8]  N. Takahashi,et al.  Complementary DNA encoding the human T-cell FK506-binding protein, a peptidylprolyl cis-trans isomerase distinct from cyclophilin. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Liu,et al.  Peptidyl-prolyl cis-trans-isomerase from Escherichia coli: a periplasmic homolog of cyclophilin that is not inhibited by cyclosporin A. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[10]  S. Schreiber,et al.  Inhibition of FKBP rotamase activity by immunosuppressant FK506: twisted amide surrogate. , 1990, Science.

[11]  M. Kaliner,et al.  Cyclosporin A inhibits degranulation of rat basophilic leukemia cells and human basophils. Inhibition of mediator release without affecting PI hydrolysis or Ca2+ fluxes. , 1990, Journal of immunology.

[12]  S. Metcalfe,et al.  CYCLOSPORINE, FK506, AND RAPAMYCIN: SOME EFFECTS ON EARLY ACTIVATION EVENTS IN SERUM‐FREE, MITOGEN‐STIMULATED MOUSE SPLEEN CELLS , 1990, Transplantation.

[13]  D. Bergsma,et al.  A second cyclophilin-related gene in Saccharomyces cerevisiae. , 1990, Nucleic acids research.

[14]  Jun O. Liu,et al.  Cloning, expression, and purification of human cyclophilin in Escherichia coli and assessment of the catalytic role of cysteines by site-directed mutagenesis. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Stein,et al.  Mechanistic studies of peptidyl prolyl cis-trans isomerase: evidence for catalysis by distortion. , 1990, Biochemistry.

[16]  N. Sigal,et al.  The immunosuppressive macrolides FK-506 and rapamycin act as reciprocal antagonists in murine T cells. , 1990, Journal of immunology.

[17]  N. Sigal,et al.  Distinct mechanisms of suppression of murine T cell activation by the related macrolides FK-506 and rapamycin. , 1990, Journal of immunology.

[18]  W. Neupert,et al.  Sensitivity to cyclosporin A is mediated by cyclophilin in Neurospora crassa and Saccharomyces cerevisiae , 1989, Nature.

[19]  G. Crabtree,et al.  Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation. , 1989, Science.

[20]  T. Hunt Cytoplasmic anchoring proteins and the control of nuclear localization , 1989, Cell.

[21]  J. Rothman Polypeptide chain binding proteins: Catalysts of protein folding and related processes in cells , 1989, Cell.

[22]  T. Starzl,et al.  FK 506 FOR LIVER, KIDNEY, AND PANCREAS TRANSPLANTATION , 1989, The Lancet.

[23]  S. Schreiber,et al.  A receptor for the immuno-suppressant FK506 is a cis–trans peptidyl-prolyl isomerase , 1989, Nature.

[24]  Nolan H. Sigal,et al.  A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin , 1989, Nature.

[25]  T. Cline The affairs of daughterless and the promiscuity of developmental regulators , 1989, Cell.

[26]  P. Katz,et al.  The effect of cyclosporine on the use of hospital resources for kidney transplantation. , 1989, The New England journal of medicine.

[27]  D. V. van Thiel,et al.  Liver transplantation (2). , 1989, The New England journal of medicine.

[28]  N. Sigal,et al.  FK-506, a potent novel immunosuppressive agent, binds to a cytosolic protein which is distinct from the cyclosporin A-binding protein, cyclophilin. , 1989, Journal of immunology.

[29]  B. Dörken,et al.  Towards a better definition of human leucocyte surface molecules. , 1989, Immunology today.

[30]  F. Dumont,et al.  The immunosuppressant FK506 selectively inhibits expression of early T cell activation genes. , 1989, Journal of immunology.

[31]  G. Fischer,et al.  Kinetic β‐deuterium isotope effects suggest a covalent mechanism for the protein folding enzyme peptidylprolyl cis/trans‐isomerase , 1989, FEBS letters.

[32]  W. Pak,et al.  Drosophila ninaA gene encodes an eye-specific cyclophilin (cyclosporine A binding protein). , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[33]  C. Zuker,et al.  The ninaA gene required for visual transduction in Drosophila encodes a homologue of cyclosporin A-binding protein , 1989, Nature.

[34]  T. Kiefhaber,et al.  Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins , 1989, Nature.

[35]  T. Hayano,et al.  Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin , 1989, Nature.

[36]  G. Crabtree Contingent genetic regulatory events in T lymphocyte activation. , 1989, Science.

[37]  K. D. Hargrave,et al.  The design and synthesis of immune regulatory agents: targets and approaches , 1989 .

[38]  B. Kahan Drug therapy: cyclosporine , 1989 .

[39]  A. Thomson FK-506--how much potential? , 1989, Immunology today.

[40]  A. Schmidt,et al.  Nuclear factors interacting with the mitogen-responsive regulatory region of the interleukin-2 gene. , 1988, The Journal of biological chemistry.

[41]  M. Harding,et al.  CYCLOPHILIN, A PRIMARY MOLECULAR TARGET FOR CYCLOSPORINE , 1988 .

[42]  G. Crabtree,et al.  Identification of a putative regulator of early T cell activation genes. , 1988, Science.

[43]  F. Dumont,et al.  A study of the correlation between cyclophilin binding and in vitro immunosuppressive activity of cyclosporine A and analogues. , 1988, Transplantation proceedings.

[44]  S. Schreiber,et al.  Is there a scaffolding domain within the structure of the immunosuppressive agent cyclosporin a (CsA)? Studies of the cyclophilin binding domain of CsA , 1988 .

[45]  F. Abe,et al.  Effects of spergualin and 15-deoxyspergualin on the development of graft-versus-host disease in mice. , 1987, Transplantation proceedings.

[46]  M. Schreier,et al.  Cyclophilin binds to the region of cyclosporine involved in its immunosuppressive activity , 1987, European journal of immunology.

[47]  D. Speicher,et al.  Cyclophilin: a specific cytosolic binding protein for cyclosporin A. , 1984, Science.

[48]  M. Liakopoulou-Kyriakides,et al.  s-Cis...and s-trans isomerism in acylproline analogs. Models for conformationally locked proline peptides. , 2009, International journal of peptide and protein research.