We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

Results: 4

1.
FIG. 1.

FIG. 1. From: Mechanism of Inhibition of Human Immunodeficiency Virus Type 1 Reverse Transcriptase by a Stavudine Analogue, 4?-Ethynyl Stavudine Triphosphate .

Chemical structures of dT, d4T, and 4′-Ed4T.

Guangwei Yang, et al. Antimicrob Agents Chemother. 2008 June;52(6):2035-2042.
2.
FIG. 3.

FIG. 3. From: Mechanism of Inhibition of Human Immunodeficiency Virus Type 1 Reverse Transcriptase by a Stavudine Analogue, 4?-Ethynyl Stavudine Triphosphate .

Single-turnover assays for determination of Kd and kpol of dTMP, d4TMP, and 4′-Ed4TMP incorporation by wt RT. (A) The observed rates of dTMP incorporation into the 23-/36-mer DNA/DNA P/T by wt RT were plotted against dTTP concentration to give a dissociation constant (Kd) of 15.4 ± 2.9 μM and a maximum rate of incorporation (kpol) of 22.6 ± 1.3 s−1. (B) The observed rates of d4TMP incorporation into the 23-/36-mer DNA/DNA P/T by wt RT were plotted against d4TTP concentration to give a Kd of 48.0 ± 4.8 μM and a kpol of 16.0 ± 0.5 s−1. (C) The observed rates of 4′-Ed4TMP incorporation into the 23-/36-mer DNA/DNA P/T by wt RT were plotted against 4′-Ed4TTP concentration to give a Kd of 15.8 ± 2.4 μM and a kpol of 12.1 ± 0.5 s−1.

Guangwei Yang, et al. Antimicrob Agents Chemother. 2008 June;52(6):2035-2042.
3.
FIG. 4.

FIG. 4. From: Mechanism of Inhibition of Human Immunodeficiency Virus Type 1 Reverse Transcriptase by a Stavudine Analogue, 4?-Ethynyl Stavudine Triphosphate .

Computer modeling of the 4′-Ed4TTP onto the wt RT-DNA/DNA-dTTP ternary complex (A) and the in silico mutated M184V-DNA/DNA-dTTP ternary complex (B). The modified nucleotide with the double bond formed between C-2 and C-3 was taken from the structure of d4TMP that bound to human thymidylate kinase (29) and superimposed onto the existing dNTP in the ternary complex. The ethynyl group was added using the standard ONO library database (16).

Guangwei Yang, et al. Antimicrob Agents Chemother. 2008 June;52(6):2035-2042.
4.
FIG. 2.

FIG. 2. From: Mechanism of Inhibition of Human Immunodeficiency Virus Type 1 Reverse Transcriptase by a Stavudine Analogue, 4?-Ethynyl Stavudine Triphosphate .

Pre-steady-state burst assays of incorporation of various nucleotides into a 23-/36-mer DNA/DNA P/T by wt RT. The kinetics were measured by mixing a preincubated solution of wt RT (200 nM) and 23-/36-mer DNA/DNA P/T (600 nM) with 2 mM nucleoside triphosphate. The polymerization reaction was quenched at defined time intervals and analyzed by gel electrophoresis. (A) Burst assay for dTMP incorporation gave an amplitude of 27.1 ± 1.2 nM; a burst rate, kob, of 12.5 ± 1.4 s−1; and a steady-state rate, kss, of 0.08 ± 0.02 s−1. (B) Burst assay for d4TMP incorporation gave an amplitude of 27.6 ± 2.0 nM; a burst rate, kob, of 10.7 ± 2.0 s−1; and a steady-state rate, kss, of 0.08 ± 0.02 s−1. (C) Burst assay for 4′-Ed4TMP incorporation gave an amplitude of 28.8 ± 1.4 nM; a burst rate, kob, of 16.2 ± 2.1 s−1; and a steady-state rate, kss, of 0.06 ± 0.03 s−1. Each data point is from a single experiment, and the figure is representative of several experiments with similar results.

Guangwei Yang, et al. Antimicrob Agents Chemother. 2008 June;52(6):2035-2042.

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Write to the Help Desk