VIPER Peptide

Experimental tool for exploring TLR4 complex formation and signalling, for analysing the role of TLR4 in in vivo models of disease and for predicting a role for Mal or TRAM in a disease process.

Contributors

Inventor Institute
Andrew Bowie Trinity College Dublin
Cat. #: 153526
Tool sub type: Synthetic Peptide
Research Fields: Drug development;Immunology;Microbiology
Product description: Overview: Toll-like receptor 4 (TLR4) recognises pathogens leading to activation of the immune response, but also contributes to the development of a number of autoimmune and in<U+FB02>ammatory diseases. As such, it has become a new target for drug development. Over millennia, viruses have optimised their ability to inhibit the immune response. Thus the Vaccinia virus protein A46 displays a remarkable ability to inhibit TLR4 function. This viral know-how has been exploited to develop an 11-amino acid peptide from A46, termed viral inhibitor peptide of TLR4, or VIPER, which, when fused to a cell-penetrating delivery sequence, potently and speci<U+FB01>cally inhibits TLR4-mediated responses in vitro and in vivo. Advantages: VIPER most likely represents a surface of A46 that has been optimised by the virus to potently inhibit TLR4, so has already been through a ‘naturally occurring drug development programme'. VIPER is more effective at inhibiting TLR4 than other currently used peptide inhibitors of TLR4, in that it is more speci<U+FB01>c, more potent, less toxic, and is effective in primary human cells. Possible Applications: Experimental tool for exploring TLR4 complex formation and signalling, for analysing the role of TLR4 in in vivo models of disease and for predicting a role for Mal or TRAM in a disease process. Development as a therapeutic agent, for example by developing it into a peptidomimetic. Analysis of surfaces on Mal and TRAM targeted by VIPER as drugable sites during in<U+FB02>ammation.
Additional notes: VIPER has been validated preclinically for e<U+FB03>cacy, with ongoing work being carried out in disease models. US patent 8,722,052
Function: Marker
References:

Lysakova-Devine et al. 2010. J Immunol. 185(7):4261-71. PMID: 20802145.

Viral inhibitory peptide of TLR4, a peptide derived from vaccinia protein A46, specifically inhibits TLR4 by directly targeting MyD88 adaptor-like and TRIF-related adaptor molecule.

Images

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Data showing inhibition of Toll-like receptor 4 (TLR4) cytokine production by viral inhibitor peptide of TLR4 (VIPER); in vitro and in vivo. Source

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