Methionine Analog Inhibitors of S-Adenosy lmethionine Biosynthesis as Potential Antitumor Agents

The essentiality of S-adenosylmethionine (AdoMet) in transmethylation reactions and polyamine biosynthesis provides a rationale for the development of methionine (Met) analog inhibitors of AdoMet synthesis as potential antitumor agents. Recent studies indicating that “Met dependent” tumors have defects in Met and AdoMet metabolism suggest that certain tumors may be particularly susceptible to growth inhibition by Met analogs (Hoffman, 1985). Systematic approaches to the design of such analogs have been facilitated by the earlier studies on Met analog inhibitors of microbial and mammalian isofunctional methionine adenosyl transferases (MAT; EC 2.5.1.6) reported by Talalay and coworkers (Chou et. al., 1977), in which certain critical features of the enzyme bound conformation of L-Met and of the complementary topography at its L-Met binding site were defined.