INHIBITORS OF TYPE-1 INTERLEUKIN-1 RECEPTOR FROM MICROBIAL METABOLITES

We describe here the results of a screening program conducted to disco ver inhibitors of the type-I interleukin-l receptor (IL-IRI) from samp les of microbial origin. An innovative approach, based on automated, n onradioactive receptor binding assays has been employed. Specially pre pared 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 activiti es have been purified and characterized. One of these, isolated from S treptomyces sp. GE48009, was identified as niphimycin, an antifungal a gent also known as scopafungin. Preliminary evidence suggests that thi s molecule and azalomycin F, a structural analogue, inhibit IL-IRI by virtue of their long-chain guanidinium moiety. The other activity, iso lated from Aspergillus sp. GE49752, was identified as flavipin, a subs tituted o-phthalaldehyde.