Tat-Beclin 1: Small Molecules and Peptides

Many standard methods to induce autophagy lack desired specificity. Both starvation and rapamycin, an allosteric inhibitor of MTORC1, are known to regulate biological processes other than autophagy. The non-specific nature of these methods complicates data interpretation and has driven the preference for loss-of-function Atg mutants to analyze autophagy. In 2013, the discovery of engineered Tat-Beclin 1 provided the first method to induce autophagy without regulating other pathways non-specifically. Peptides composed of the autophagy-inducing region of Beclin 1 fused to the HIV-Tat protein were demonstrated to increase autophagosome and autolysosome numbers, as well as protein degradation. Since then, Tat-Beclin 1 peptides have been widely used to successfully induce autophagy both in vitro and in vivo. The peptides below are of a shorter Tat-Beclin 1 peptide with an enhanced potency to induce autophagy. This shorter peptide, Tat-D11, increases autophagosome and autolysosome induction by over fivefold compared to the longer peptide, Tat-Beclin 1. Results have demonstrated the superior potency of Tat-D11 over Tat-Beclin 1.