The antifungal antibiotic sinefungin as a ver y active inhibitor of methyltransferases and of the transformation of chick embryo fibroblasts by rous sarcoma virus

Abstract

The antifungal antibiotic Sinefungin is a structural analogue of S-adenosyl-methionine (SAM) and of S-adenosyl-homocysteine (SAH). It is as active as the synthetic SAH analogue S-isobutyl adenosine (SIBA) in inhibiting Rous Sarcoma Virus (RSV) induced transformation of chick embryo fibroblasts (CEF) in cell culture. Sinefungin, like SAH and SIBA is a competitive inhibitor in vitro of tRNA methylases and of protein methylases I and III of CEF. Its ki value for tRNA methylases of normal and transformed cells is respectively 3 to 10 times lower than the ki of SAH. It is thus in vitro the most active tRNA methylase inhibitor described until now. Protein methylase I and III are inhibited to about the same extent by the two molecules whereas SIBA has much higher ki values for the three enzymes in vitro. When methylation was measured in whole cells SAH, SIBA and Sinefungin inhibited (14C)-methyl incorporation to about the same degree in normal cells, but only SIBA and Sinefungin were active in transformed cells.{A figure is presented}. © 1978 Academic Press, Inc.