CL429 - TLR2 & NOD2 Bispecific Agonist

TLR2-NOD2 Ligand - Pam2C-conjugated murabutide

CL429 is a chimeric compound that stimulates TLR2 and NOD2 [1]. This compound is composed of murabutide (NOD2 ligand) covalently linked to Pam2C (TLR2 ligand) via a spacer. Murabutide is derived from muramyl dipeptide (MDP), the smallest bioactive unit of bacterial peptidoglycan. Murabutide is recognized by the cytosolic sensor NOD2, which induces the activation of NF-κB through the adaptor RIP2 [2.] Pam2C is the lipid moiety of Pam2CSK4, which is recognized by the cell surface receptor TLR2 leading to the activation of NF-κB through the adaptor MyD88 [3]. NOD2 and TLR2 have been shown to exert synergistic effects on the production of cytokines [4-6]. CL429 was reported to possess a very potent adjuvant activity, with no apparent toxicity [1].

CL429 induces the activation of NF-κB in HEK-Blue™ TLR2 cells and HEK-Blue™ NOD2 cells, as well as in RAW-Blue™ cells, which express both TLR2 and NOD2.

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References:

1. Pavot V. et al., 2014. Cutting edge: New chimeric NOD2/TLR2 adjuvant drastically increases vaccine immunogenicity. J Immunol. 193(12):5781-5.
2. Jakopin Ž., 2013. Murabutide revisited: a review of its pleiotropic biological effects. Curr Med Chem. 20(16):2068-79.
3. Buwitt-Beckmann U. et al., 2005. Toll-like receptor 6-independent signaling by diacylated lipopeptides. Eur J Immunol. 35(1):282-9.
4. Moreira L.O. et al., 2008. The TLR2-MyD88-NOD2-RIPK2 signalling axis regulates a balanced pro-inflammatory and IL-10-mediated anti-inflammatory cytokine response to Gram-positive cell walls. Cell Microbiol. 10(10):2067-77.
5. Jeong Y.J. et al., 2014. Nod2 and Rip2 contribute to innate immune responses in mouse neutrophils. Immunology. 143(2):269-76.
6. Trinchieri G. & Sher A., 2007. Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol. 7(3):179-90