The taming of the cell penetrating domain of the HIV Tat: myths and realities.
Protein transduction with cell penetrating peptides over the past several years has been shown to be an effective way of delivering proteins in vitro and now several reports have also shown valuable in vivo applications in correcting disease states. An impressive bioinspired phenomenon of crossing biological barriers came from HIV transactivator Tat protein. Specifically, the protein transduction domain of HIV Tat has been shown to be a potent pleiotropic peptide in protein delivery. Various approaches such as molecular modeling, arginine guanidinium head group structural strategy, multimerization of PTD sequence and phage display system have been applied for taming of the PTD. This has resulted in identification of PTD variants which are efficient in cell membrane penetration and cytoplasmic delivery. In spite of these state of the art technologies, the dilemma of low protein transduction efficiency and target specific delivery of PTD fusion proteins remains unsolved. Moreover, some misconceptions about PTD of Tat in the literature require considerations. We have assembled critical information on secretory, plasma membrane penetration and transcellular properties of Tat and PTD using molecular analysis and available experimental evidences.
Chauhan
Ashok
A
Department of Neurology, Richard Johnson Division of Neuroimmunology and Neurological Infections, Johns Hopkins University, 509 Pathology, Baltimore, MD 21287, USA. achauha1@jhmi.edu
Tikoo
Akshay
A
Kapur
Arvinder K
AK
Singh
Mahavir
M
D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods; D004705:Endocytosis; D015696:Gene Products, tat / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000378:metabolism*
D015696:Gene Products, tat; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins