Synthetic protein transduction domains: Enhanced transduction potential invitro and in vivo

The protein transduction domain (PTD) embedded in the HIV TAT protein (amin o acids 47-57) has been shown to successfully mediate the introduction of h eterologous peptides and proteins in excess of M-r 100,000 into mammalian c ells in vitro and irt vivo. We report here that the modeled structure of th e TAT PTD is a strong amphipathic helix, On the basis of this information, we synthesized a series of synthetic PTDs that strengthen the or-helical co ntent and optimize the placement of arginine residues. Several PTD peptides possessed significantly enhanced protein transduction potential compared w ith TAT in vitro and in vivo. These optimized PTDs have the potential to de liver both existing and novel anticancer therapeutics.