Inhibitors of type-I interleukin-1 receptor from microbial metabolites.
We describe here the results of a screening program conducted to discover inhibitors of the type-I interleukin-1 receptor (IL-1RI) from samples of microbial origin. An innovative approach, based on automated, nonradioactive receptor binding assays has been employed. Specially prepared cell-free systems have allowed the use of high concentrations of microbial metabolites in the reaction mixtures with a low percentage of false positives. More than 30,000 microbial samples from different species of soil isolates have been tested and two interesting activities have been purified and characterized. One of these, isolated from Streptomyces sp. GE48009, was identified as niphimycin, an antifungal agent also known as scopafungin. Preliminary evidence suggests that this molecule and azalomycin F, a structural analogue, inhibit IL-IRI by virtue of their long-chain guanidinium moiety. The other activity, isolated from Aspergillus sp. GE49752, was identified as flavipin, a substituted o-phthalaldehyde.[1]References
- Inhibitors of type-I interleukin-1 receptor from microbial metabolites. Stefanelli, S., Corti, E., Montanini, N., Denaro, M., Sarubbi, E. J. Antibiot. (1997) [Pubmed]
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