Tat-3L4F is a peptide constructed by fusing the 3L4F peptide, a segment of the third intracellular loop of the human 5-HT2C receptor (3L4F refers to third loop, fourth fragment) to the cell-penetrant TAT peptide. The 3L4F fragment, Pro280 -Arg295, is a key interface for interaction between the 5-HT2C receptor and the phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10), and accordingly Tat-3L4F rapidly and potently disrupts the 5-HT2CR -PTEN interaction in CHO cells. In vitro, Tat-3L4F allosterically augments 5-HT2C mediated signaling in live cells and possesses 5-HT2C receptor agonist like properties, functioning as a positive allosteric modulator. In behavioural tests, Tat-3L4F blocks the conditioned place preference of THC and nicotine, and in olanzapine fed rats it attenuates hyperphagia and weight gain.In some studies Tat-3L4F has been used as the N terminal acetyl and C terminal amide and this variant can be supplied on request.
