- Name Andrew Bowie
- Institute Trinity College Dublin
Tool name: VIPER Peptide
Tool type: Proteins
Tool sub-type: Synthetic Peptide
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 inammatory 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 specically inhibits TLR4-mediated responses in vitro and in vivo.
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 specic, more potent, less toxic, and is effective in primary human cells.
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 inammation.
Research area: Drug Discovery & Development ; Immunology ;
- For Research Use Only
- • 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.