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Table 4 Formation of DEC or DEC-like complex by ddNTP-terminated DNA and HIV-1 RT in the presence of next correct dNTP, ddNTP or EFV.

From: The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study

Dideoxyadenosine analog as the chain-terminator

   

Next Correct dNTP or ddNTP

  

EFV

 

DNA

Terminator

 

dCTP

  

FTC-TP

    
  

Kd (μM)

Bmax (%)

Bmax/Kd

Kd (μM)

Bmax (%)

Bmax/Kd

Kd (μM)

Bmax (%)

Bmax/Kd

D20/D36

TFV

232 ± 12a

18.5 ± 6.7

0.079

250 ± 11

17.7 ± 3.9

0.071

0.70 ± 0.10

45.7 ± 10.0

65

 

ddAMP

21.5 ± 9.8

34.2 ± 4.6

1.6

171 ± 28

28.1 ± 4.7

0.16

1.20 ± 0.38

16.3 ± 3.5

13.6

D26/D50

TFV

179 ± 33

50.0 ± 5.5

0.28

46.5 ± 7.8

50.0 ± 5.0

1.1

1.22 ± 0.28

44.4 ± 3.7

36

 

ddAMP

8.1 ± 2.1

55.8 ± 3.4

6.9

86.8 ± 0.2

60.2 ± 7.2

0.69

2.42 ± 1.10

11.2 ± 0.6

4.6

Dideoxycytidine analog as the chain-terminator

   

Next Correct dNTP or ddNTP

  

EFV

 

DNA

Terminator

 

dATP

  

TFV-DP

    
  

Kd (μM)

Bmax (%)

Bmax/Kd

Kd (μM)

Bmax (%)

Bmax/Kd

Kd (μM)

Bmax (%)

Bmax/Kd

D20/D36

FTC-MP

NDa

ND

ND

ND

ND

ND

1.54 ± 0.33

5.53 ± 1.83

3.0

 

ddCMP

16.9 ± 8.5

38.0 ± 4.4

2.2

445 ± 114

15.3 ± 2.7

0.034

1.03 ± 0.25

14.9 ± 0.8

14.5

D27/D50

FTC-MP

862 ± 229

45 ± 14

0.052

ND

ND

ND

1.26 ± 0.24

3.96 ± 1.55

3.1

 

ddCMP

6.5 ± 2.6

60 ± 3

9.2

140 ± 19

55 ± 2

0.39

0.11 ± 0.06

10.6 ± 2.0

96

  1. All Values reported are average ± standard deviation from at least three measurements.
  2. aND = No DEC formation was detected at the highest concentration (2 mM) tested.