For a smaller pack size, please see Prod. No. ALX-746-253
Inhibitory iODN oligodeoxynucleotide with phosphorothioate backbone. Economical minimal active sequence of a potent inhibitory ODN for in vivo use in rodents (50-150µg per injection), based on prototype class I (ODN 2088/2114), may also affect TLR7 and TLR8 signaling.
|Sequence:||5’-tcctggagggg-3’(lower case letters indicate phosphorothioate linkage).|
|MW:||3583 (ammonium salt)|
|Quantity:||~280nmol (1'000µg). Working concentration depends upon concentration, type and MW of stimulating CpG ODN, the cellular system and read-out used. Titrate at 3-5 fold molar excess for inhibition.|
|Endotoxin Content:||<0.002EU/µg |
|Reconstitution:||For a 200µM stock solution, dissolve the total vial content in 1'400µl endotoxin-free ddWater (Prod. No. ALX-505-008) or endotoxin-free PBS (Prod. No. ALX-505-007). To obtain optimal dissolving we recommend the following procedure:|
- Add 50% of the solvent and let dissolve for 10 min.
- Add remaining 50% of the solvent and mix thoroughly.
- Moderate warming may aid dissolving.
|Long Term Storage:||+4°C|
|Use/Stability:||Aqueous stock solution is stable for 1 day when stored at +4°C.|
|Handling:||Protect from light. For maximum product recovery after thawing, centrifuge the vial before opening the cap. After reconstitution, prepare aliquots and store at -20°C.|
|Scientific Background:||Several groups have studied the sequence requirements, specificity, signalling pathways and kinetics of the TLR (Toll-like receptor) 9 suppression by ‘inhibitory DNA motifs’, which led to a revised classification of iODNs, that is independent of the previously thought species preference.Class I: G-stretch ODNs: TLR9-specific competitors, some iODNs may also affect TLR7 and TLR8 signalingClass II: ODNs with telomeric repeats: TLR-independent inhibitors of STAT signalling (cellular uptake via an “ODN receptor”?)Class III: Inhibitors of DNA uptake in a sequence independent mannerClass IV: Long phosphorothioate ODNs as direct competitors of TLR9 signaling in a sequence independent mannerSlightly modified phosphodiester versions of the most potent inhibitory ODNs were also able to profoundly block the immune activation of macrophages and proved to be valuable tools for in vivo use in experimental animal models of inflammatory and auto-immune diseases.|
|Technical Info/Product Notes:||Includes 1 vial of ddWater (endotoxin-free) (Prod. No. ALX-505-008).|
For active CpG compounds, please see Prod. No. ALX-746-001.
Product Literature References
Sequence requirements for oligodeoxyribonucleotide inhibitory activity
: R.F. Ashman, et al.; Int. Immunol. 17
, 411 (2005), Abstract
General Literature References
DNA motifs suppressing TLR9 responses
: A. Trieu; Crit. Rev. Immunol. 26
, 527 (2006), Abstract
Inhibitors of TLR-9 act on multiple cell subsets in mouse and man in vitro and prevent death in vivo from systemic inflammation
: O. Duramad, et al.; J. Immunol. 174
, 5193 (2005), Abstract
Inhibitory oligodeoxynucleotides - therapeutic promise for systemic autoimmune diseases?
: P. Lenert; Clin. Exp. Immunol. 140
, 1 (2005), Abstract
Suppressive oligodeoxynucleotides protect mice from lethal endotoxic shock
: H. Shirota, et al.; J. Immunol. 174
, 4579 (2005), Abstract
Therapeutic potential of oligonucleotides expressing immunosuppressive TTAGGG motifs
: D.M. Klinman, et al.; Ann. NY Acad. Sci. 1058
, 87 (2005), Abstract
Immunotherapeutic utility of stimulatory and suppressive oligodeoxynucleotides
: K.J. Ishii, et al.; Curr. Opin. Mol. Ther. 6
, 166 (2004), Abstract
Suppressive oligodeoxynucleotides inhibit Th1 differentiation by blocking IFN-gamma- and IL-12-mediated signaling
: H. Shirota, et al.; J. Immunol. 173
, 5002 (2004), Abstract
Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation
: I. Gursel, et al.; J. Immunol. 171
, 1393 (2003), Abstract