HIV-1 REVERSE-TRANSCRIPTASE IS CAPABLE OF ELONGATING DERIVATIVES OF SEQUENCE-SPECIFIC NONCOMPLEMENTARY OLIGODEOXYNUCLEOTIDES

We have carried out a comparison of K-M and V-max values for various p rimers in the polymerization reaction catalyzed by the HIV-I RT. The a ffinity of RT for complementary d(pT)(6) containing two different 5'-e nd pyranone derivatives was 2-3 orders of magnitude higher (K-M = 3-15 nM) than that of d(pT)(6) (K-M = 12.6 mM). Oligodeoxynucleotides (ODN s) noncomplementary to poly(A) template were not elongated by RT. Howe ver, derivatives of d(CAGGTG) containing the 5'-terminal chromone and coumarin related groups were efficient primers showing K-M (30-300 nM) and V-max (75-93 %) values comparable with that for d(pT)lo (800 nM; 100%). The [d(CAGGTG)]ddT ODN derivatives were effective inhibitors of RT. The primer function of derivatives of noncomplementary ODNs appea rs to be due to the additional interactions of their 5'-terminal group s with the enzyme tRNA-binding site.