[Interaction of HIV-1 reverse transcriptase with new minor groove ligands and their conjugates with oligonucleotides].
The influence of new non-natural regular minor groove binders (MGB), containing 2-4 imidazole, pyrrole or thiazole residues, and their conjugates with oligonucleotides, on the polymerization reaction catalyzed by HIV-1 reverse transcriptase was analyzed. Various model template-primer complexes: poly(A)-oligo(U), poly(A)-oligo(dT), poly(dA)-oligo(U), poly(dA)-oligo(dT) and activated DNA were used. The concentration of oligopeptides, giving 50% inhibition (I50) of the RT-dependent polymerization reaction, was shown to depend strongly on the structure of template-primer complexes, number and type of the heterocycle rings in the MGBs analyzed. The range of I50 for the most of the compounds studied is 7.7 x 10(-3)-1.0 x 10(-5) M. The affinity of MGB is minimal for poly(A)-oligo(U). However, some of imidazole and pyrrole-containing MGBs demonstrated unusually high affinity (I50 = 3 x 10(-9)-4 x 10(-8) M) to the above template-primer in complex with RT. The affinity of conjugates of thiazolecarboxamides with oligonucleotides complementary or partially complementary to the template, is 1-4 orders higher compared to free thiazolecarboxamides. The possible reasons of the dependence of I50 values upon the structure of the template-primer complexes, the structure of MGB, and their conjugates with oligonucleotides are discussed.
Zakharova
O D
OD
Baranova
S V
SV
Riabinin
V A
VA
Siniakov
A N
AN
Iamkovoĭ
V I
VI
Tarrago-Litvak
L
L
Litvak
S
S
Nevinskiĭ
G A
GA
D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008024:Ligands; D009841:Oligonucleotides / Q000737:chemistry*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry*
D008024:Ligands; D009841:Oligonucleotides; D018894:Reverse Transcriptase Inhibitors; D013844:Thiazoles; D054303:HIV Reverse Transcriptase