2'-C-Methyladenosine Chemical Properties

Boiling point:

643.4±65.0 °C(Predicted)

Density 

1.89

storage temp. 

Store at -20°C

solubility 

DMF: 5 mg/mL; DMSO: 20 mg/mL; PBS (pH 7.2): 10 mg/mL

form 

A crystalline solid

pka

13.18±0.70(Predicted)

color 

White to off-white

InChI

InChI=1S/C11H15N5O4/c1-11(19)7(18)5(2-17)20-10(11)16-4-15-6-8(12)13-3-14-9(6)16/h3-5,7,10,17-19H,2H2,1H3,(H2,12,13,14)/t5-,7-,10-,11-/m1/s1

InChIKey

PASOFFRBGIVJET-YRKGHMEHSA-N

SMILES

OC[C@H]1O[C@@H](N2C3C(=C(N=CN=3)N)N=C2)[C@](C)(O)[C@@H]1O

2'-C-Methyladenosine Usage And Synthesis

Description

2′-C-Methyladenosine has been shown to inhibit HCV RNA replication in the absence of cytotoxicity. The corresponding triphosphates were shown to be potent, competitive inhibitors of NS5B-catalyzed reactions in vitro.

Uses

2'-C-Methyladenosine is an inhibitor of hepatitis C virus (HCV) replication. 2'-C-Methyladenosine inhibits HCV replicon and NS5B-catalyzed RNA synthesis with IC50 values of 0.3μM and 1.9 μM, respectively. 2'-C-Methyladenosine also potently inhibits LRV1 in Leishmania guyanensis (Lgy) and Leishmania braziliensis[1][2].

Biological Activity

2’-C-Methyladenosine is an inhibitor of hepatitis C virus (HCV) replication (IC50 = 0.3 μM in Huh-7 human hepatoma cells) that is not cytotoxic at concentrations up to 100 μM.{39652} It is converted intracellularly to adenosine triphosphate, which inhibits the RNA-dependent RNA polymerase nonstructural protein 5B (NS5B). It also inhibits growth of L. guyanensis in vitro (EC50 = 3 μM) and eradicates it when used at a concentration of 10 μM.

Synthesis

Synthesis of yfl-2'-methyl-adenosine (CHCl); N6-tert-butanoyl-/?-2'-methyl-2',3',5'-tribenzoyl-adenosine (400 mg, 0.590 mmol) was added to a solution of MeOH saturated with ammonia, and stirred at room temperature. After 12 hours the solvent was removed and the obtained solid was purified by column chromatography in gradient starting with a mixture of CHCl3/MeOH 9:1 then 8:2. The pure product was obtained as a white solid (120 mg, 0.427 mmol, 72%). |?H (J6-DMSO): 8.47 (IH, s, H8-adenosine), 8.15 (IH, s, H2-adenosine), 7.30 (IH, s, NH26-adenosine), 5.95 (IH, s, Hl '-adenosine), 5.25-5.21 (3H, m, OH5' -adenosine, OH3'- adenosine, OH2' -adenosine), 4.12-4.05 (IH, d, H3 '-adenosine, J= 8.6 Hz), 3.91 (IH, m, H4'-adenosine), 3.84 (IH, m, H5' -adenosine), 3.70 (IH, m, H5' -adenosine), 0.77 (3H3 s, CH32'-adenosine); |?c (4-DMSO): 156.02 (1C, C6-adenosine), 152.53 (1C, C2-adenosine), 149.01 (1C, C4-adenosine), 138.68 (1C, C8-adenosine), 118.67 (1C, C5-adenosine), 90.78 (1C, Cl '-adenosine), 82.52 (1C, C4' -adenosine), 78.46 (1C, C2'-adenosine), 71.63 (1C, C3' -adenosine), 59.47 (1C, C5 '-adenosine), 19.83 (1C, CH3-2'-adenosine). Anal. CaIc. for C11H15N5O4: C 46.97%, H 5.38%, N 24.90%. Found: C 46.67%, H 5.22%, N 24.20%.

in vivo

References

[1] Steven S Carroll, et al. Inhibition of hepatitis C virus RNA replication by 2'-modified nucleoside analogs. J Biol Chem. 2003 Apr 4;278(14):11979-84. DOI:10.1074/jbc.M210914200
[2] John I Robinson, et al. Concentration of 2'C-methyladenosine triphosphate by Leishmania guyanensis enables specific inhibition of Leishmania RNA virus 1 via its RNA polymerase. J Biol Chem. 2018 Apr 27;293(17):6460-6469. DOI:10.1074/jbc.RA117.001515

2'-C-Methyladenosine(15397-12-3)Related Product Information

• EC 3.5.4.4
• 5'-Deoxyadenosylcobalamin
• Cyclic AMP
• S-ADENOSYL-L-METHIONINE
• ADENOSINE 5'-TRIPHOSPHATASE
• Adenosine5'-(tetrahydrogen triphosphate), disodiuM salt, trihydrate (9CI)
• Vidarabine
• 2'-C-Methylguanosine
• 2'-C-Methylcytidine
• 2'-C-Methyladenosine