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iODN 2088 (class I) (endotoxin-free) (synthetic)

 
ALX-746-250-T050 50 tests 183.00 USD
Do you need bulk/larger quantities?
 
For a larger pack size, please see Prod. No. ALX-746-350.
Inhibitory iODN oligodeoxynucleotide with phosphorothioate backbone. Potent sequence of an inhibitory ODN for in vivo use in rodents (50-150µg per injection): prototype class I, may also affect TLR7 and TLR8 signaling.

Product Specification

Sequence:5’-tcctggcggggaagt-3’ (lower case letters indicate phosphorothioate linkage).
 
MW:4887 (ammonium salt)
 
Source:Synthetic.
 
Quantity:40nmol (~200µg). Sufficient for ~50 cellular inhibition assays. Working concentration depends upon concentration, type and MW of stimulating CpG ODN, the cellular system and read-out used. Titrate at 3-10 fold molar excess for inhibition.
 
Formulation:Lyophilized. Sterile.
 
Endotoxin Content:<0.002EU/µg
 
Reconstitution:For a 100µM stock solution, dissolve the total vial content in 400µl endotoxin-free water (included) or PBS (to order separately).
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.
 
Shipping:Ambient
 
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 signaling
Class 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 manner
Class IV: Long phosphorothioate ODNs as direct competitors of TLR9 signaling in a sequence independent manner
Slightly 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.
 
746-250
Figure: ODN 1668 (TLRgrade™) (synthetic) (Prod. No. ALX-746-001) was added at 50pM/ml to macrophages in a 96-well plate simultaneously together with iODN 2088 (TLRgrade™) (synthetic) (Prod. No. ALX-746-250) at the indicated molar excess, cell supernatants harvested after 24 hours and IL-12-p40 analyzed by cytokine ELISA. Similar inhibition rates of >90 (3:1 molar excess) or >95% (10:1) were observed with iODN 2088 (TLRgrade™) and CpG ODN 1668 (TLRgrade™), when analyzed for IL-6.
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746-250

Product Literature References

The elucidation of gene transferring mechanism by ultrasound-responsive unmodified and mannose-modified lipoplexes: K. Un, et al.; Biomaterials 32, 4659 (2011), Abstract;
Toll-like receptor 9 inhibition reduces mortality in polymicrobial sepsis: G. Plitas, et al.; J. Exp. Med. 205, 1277 (2008), 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;

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