Studies on amikhellin. II.-Inhibition of dna-polymerase from murine sarcoma leukemia virus.

We have previously reported that amikhellin binds to double-stranded DNA by an intercalation process (1). We now report that this drug inhibits the DNA-polymerase from murine sarcoma leukemia virus. The extent of inhibition was found to vary with the nature of the primer-template used : maximum with poly(rA)n-oligo(dT)10 (nucleotide ratio 20:1), minimum with poly(rA)n-poly(dT)n and intermediate with native calf thymus DNA. Experiments performed with synthetic templates of the (rA)-(dT) type have led to the following conclusions as to the mechanism of inhibition: 1) Amikhellin acts at an early stage of the synthesis reaction because the drug is no longer inhibitory when a limited extension of the oligo(dT) primers has been allowed to occur. However, mere incubation of the enzyme with the template in the absence of dTTP is not sufficient to confer resistance to the drug. 2) Progression of enzyme molecules actively engaged in polymerization is stopped when they reach downstream duplex regions to which amikhellin is bound.