Table 1

Analysis of 2–5A analogues

CompoundChemical structure2–5A Binding activityaRNase L activity in vitrobRNase L activity in vivocStability in human serum (T1/2, h)
Human cellsMouse cells
Natural phosphodiester 2–5A
 1ppp5′A(2′p5′A)2+++++++++NT
 2ppp5′A2′p5′ANTNT
 3p5′A(2′p5′A)3++++++NTNT1.24
Phosphorothioate mixed isomer (Rp+ Sp)
 4ps5′A(2′ps5′A)3+++++++++++++>24
Phosphorothioate mixed isomer (Rp+ Sp) with 2′/3′-terminal modification
 5ps5′A(2′ps5′A)32′-OCH3++++++++NTNT
 6ps5′A2′ps5′A2′ps3′dCNTNTNT
 7ps5′A(2′ps5′A)22′ps3′dC+++++++++++>24
 8ps5′A(2′ps5′A)22′ps3′dG++++++++++++NT
  • a Competitive inhibition of binding to GST-RNase L to radiolabeled 2–5A probe at: 1 nm, +++; 10 nm, ++; 100 nm, +; none at 100 nm, −.

  • b Assayed with recombinant RNase L against C7U2C12, active [>50% cleavage of RNA] at: 0.1 nm, ++++; 1 nm, +++; 10 nm, ++; 100 nm, +; none at 100 nm.

  • c Assayed in human Hey1b cells or mouse L929 cells, 1 μm compound transfected for 3 h, percentage rRNA cleavage: 70–80%, ++++; 60–70%, +++; 50–60%, ++; <50%, +; none, −; NT, not tested.