TAT-TRPV1 (736-745) – TAT Conjugated Peptides

TAT-TRPV1 (736-745) is a cell-permeable TRPV1 fragment (capsaicin receptor and the vanilloid receptor 1), that can inhibit the interaction of TRPV1 and A-kinase anchoring protein 79 (AKAP79). TAT- TRPV1 (736-745) consists of amino acids 736-749 from the TRPV1 C-terminal domain, combined with amino acids 47-57 of TAT to promote uptake across neuronal cell membranes. TAT-TRPV1 (736-745) inhibits both the first and the second phase of pain behaviour in the formalin test, implying an effect on both acute and inflammatory pain. A-kinase anchoring protein 79 (AKAP79) is a protein that targets kinases to TRPV1. Inflammation causes hyperalgesia but can be reduced when TRPV1 is blocked. a key region on AKAP79, amino acids 326-336, is responsible for its interaction with TRPV1. TAT-TRPV1 (736-745) promotes uptake across the cell membrane and TRPV1 (736-745)  inhibited inflammatory hyperalgesia in mice. TAT-TRPV1 (736-745) did not affect pain thresholds in the absence of inflammation. These results suggest that antagonizing the TRPV1-AKAP79 interaction will be a useful strategy for inhibiting inflammatory hyperalgesia and TAT is an effective delivery system.

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