Interaction of HIV-1 reverse transcriptase with modified oligonucleotide primers containing 2'-O-beta-D-ribofuranosyladenosine

• Published in: Biochemistry (Moscow) Vol. 69; no. 2; pp. 130 - 136
• Main Authors: Golubeva, A S, Ermolinsky, B S, Efimtseva, E V, Tunitskaya, V L, van Aerschot, A, Herdewijn, P, Mikhailov, S N, Kochetkov, S N
• Format: Journal Article
• Language: English
• Published: United States Springer 01-02-2004
• Subjects: Adenosine - analogs & derivatives; Adenosine - chemistry; Adenosine - metabolism; Analysis; Binding Sites; DNA microarrays; DNA Primers - chemistry; DNA Primers - metabolism; DNA Replication; Health aspects; HIV infection; HIV Reverse Transcriptase - antagonists & inhibitors; HIV Reverse Transcriptase - chemistry; HIV Reverse Transcriptase - metabolism; HIV-1 - enzymology; Humans; Models, Chemical; Protein Binding; Reverse transcriptase; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - metabolism; RNA; Synthesis; Virus Replication; Russia
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1023/B:BIRY.0000018942.76948.b0

Modified synthetic oligodeoxyribonucleotides containing 2'-O-beta-D-ribofuranosyladenosine were used as primers in the RNA-dependent DNA synthesis catalyzed by HIV-1 reverse transcriptase. The degree of elongation of the primers depends on the position of the additional ribose unit, its presence in the specific position of the primer (-4) (and only in it) completely preventing elongation. Computer-modeled binding of the modified primers to the active site of reverse transcriptase demonstrated that steric hindrances arising from the interaction of the additional ribose residue with the reverse transcriptase region 262-270 interacting with the minor groove of the DNA substrate prevents elongation in the above mentioned case.