Gregory A. Rener

Tubulin Binding Properties of Two Chiral Isomers with 1-Deaza-7, 8-Dihydropteridine Structure

It has been shown that ethyl 5-amino-l,2-dihydro-2-methyl-3-phenyl pyrido (3,4-b)pyrazin-7-yl carbamate (NSC 370147) inhibits microtubule formation, that this racemic compound binds to tubulin at or near the colchicine site, and that it enhances the binding of Vincristine to tubulin1. It appeared of interest to evaluate the activity of the R-enantiomer (NSC 613863) and the S-enantiomer (NSC 613862, CI 980). Hence, their interactions were examined at molecular level. Furthermore, we compared the binding properties of these new compounds to those of colchicine and colchicine analogues, which are firmly established. The influence of chirality on the polymerization of microtubule proteins and tubulin is also discussed.