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Microbiology (Reading) ; 154(Pt 7): 1973-1979, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18599825

RESUMO

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.


Assuntos
Antifúngicos/isolamento & purificação , Araceae/microbiologia , Colletotrichum/imunologia , Imunossupressores/isolamento & purificação , Micoses/microbiologia , Peptídeos/isolamento & purificação , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Bioensaio , Células Sanguíneas/efeitos dos fármacos , Colletotrichum/isolamento & purificação , Colletotrichum/ultraestrutura , Ciclosporina/farmacologia , Fungos/efeitos dos fármacos , Humanos , Imunossupressores/química , Imunossupressores/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular , Interleucina-2/imunologia , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Micoses/tratamento farmacológico , Peptídeos/química , Peptídeos/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
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