MIMOSINE INHIBITS VIRAL-DNA SYNTHESIS THROUGH RIBONUCLEOTIDE REDUCTASE

The plant amino acid mimosine (beta-N(3-hydroxy-4-pyridone)-alpha-amin o propionic acid) is toxic for animals and reversibly inhibits the rep lication of animal cells in vitro. We have found that mimosine inhibit s the DNA synthesis of a variety of DNA viruses, including adenovirus, parvovirus, and papovavirus and the replication of vaccinia and herpe s simplex virus 1 in cells in culture. However, mimosine did not inhib it the replication of SV40 DNA in a cell-free system. Because mimosine inhibition of viral DNA synthesis was reversible by iron in the mediu m, we hypothesized that mimosine was inhibiting ribonucleotide reducta se through its capacity to chelate the iron required in the R2 subunit of this enzyme. In support of this hypothesis, we found that mimosine -treated cells had a reduction in the pools of dGTP and dATP and that mimosine inhibited ribonucleotide reductase in vitro in an iron-depend ent manner. (C) 1994 Academic Press, Inc.