Colutellin A, an immunosuppressive peptide from Colletotrichum dematium.
Colletotrichum dematium is an endophytic fungus recovered from a Pteromischum sp. growing in a tropical forest in Costa Rica. This fungus makes a novel peptide antimycotic, colutellin A, with a MIC of 3.6 microg ml(-1) (48 h) against Botrytis cinerea and Sclerotinia sclerotiorum. Collutellin A has a mass of 1127.7 Da and contains residues of Ile, Val, Ser, N-methyl-Val and beta-aminoisobutryic acid in nominal molar ratios of 3 : 2 : 1 : 1 : 1, respectively. Independent lines of evidence suggest that the peptide is cyclic and sequences of Val-Ile-Ser-Ile and Ile-Pro-Val have been deduced by MS/MS as well as Edman degradation methods. Colutellin A inhibited CD4(+) T-cell activation of interleukin 2 (IL-2) production with an IC(50) of 167.3+/-0.38 nM, whereas cyclosporin A in the same test yielded a value of 61.8 nM. Inhibition of IL-2 production by collutellin A at such a low concentration indicates the potential immunosuppressive activity of this compound. In repeated experiments, cyclosporin A at or above 8 microg ml(-1) exhibited high levels of cytotoxicity on human peripheral blood mononuclear cells, whereas collutellin A or DMSO (carrier) alone, after 24 and 48 h of culture, exhibited no toxicity. Because of these properties collutellin A has potential as a novel immunosuppressive drug.
Ren
Yuhao
Y
Department of Plant Sciences, Montana State University, Bozeman, MT 59717, USA.
Strobel
Gary A
GA
Department of Plant Sciences, Montana State University, Bozeman, MT 59717, USA.
Graff
Jill C
JC
Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717, USA.
Jutila
Mark
M
Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717, USA.
Park
Sung Gyoo
SG
Departments of Immunobiology and Molecular Biophysics & Biochemistry, Yale University School of Medicine, S625A, The Anlyan Center (TAC), 300 Cedar Street, New Haven, CT 06520, USA.
Gosh
Sankar
S
Departments of Immunobiology and Molecular Biophysics & Biochemistry, Yale University School of Medicine, S625A, The Anlyan Center (TAC), 300 Cedar Street, New Haven, CT 06520, USA.
Teplow
David
D
Department of Neurology, David Geffen School of Medicine and Molecular Biology Institute and Brain Research institute, University of California, Los Angeles, CA 90095, USA.
Condron
Margaret
M
Department of Neurology, David Geffen School of Medicine and Molecular Biology Institute and Brain Research institute, University of California, Los Angeles, CA 90095, USA.
Pang
Eric
E
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA.|Department of Neurology, David Geffen School of Medicine and Molecular Biology Institute and Brain Research institute, University of California, Los Angeles, CA 90095, USA.
Hess
Wilford M
WM
Department of Plant and Animal Biology, Brigham Young University, Provo, UT 94602, USA.
Moore
Emily
E
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D029064:Araceae / Q000382:microbiology*; D001419:Bacteria / Q000187:drug effects; D001681:Biological Assay; D001773:Blood Cells / Q000187:drug effects; D020231:Colletotrichum / Q000276:immunology* / Q000302:isolation & purification / Q000648:ultrastructure; D016572:Cyclosporine / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D007376:Interleukin-2 / Q000276:immunology; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009181:Mycoses / Q000188:drug therapy / Q000382:microbiology*; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D036341:Intercellular Signaling Peptides and Proteins; D007376:Interleukin-2; D010455:Peptides; C531374:colutellin A; D016572:Cyclosporine