TITLE:
Role of Tat-Mediated PDZ Peptide Delivery in Pain Therapy
AUTHORS:
Haiying Wu, Feng Tao
KEYWORDS:
Tat Peptides, Protein Transduction Domain, Protein Interactions, PDZ Domains, Chronic Pain
JOURNAL NAME:
Journal of Biomaterials and Nanobiotechnology,
Vol.2 No.5,
December
9,
2011
ABSTRACT: Delivery of therapeutic peptides or proteins into tissues is severely limited by the size and biochemical properties of the molecules. Protein transduction domain (PTD)-mediated cargo transduction represents a novel and promising strategy to deliver biologically active peptides in vivo. The first PTD was identified from the HIV-1 transactivating transcriptional activator protein Tat in 1988. Since then, other PTDs have also been identified, including the third α-helix of the antennapedia homeotic transcription factor and synthetic peptide carriers. However, Tat PTD (amino acids 47 - 57) has shown markedly better ability for intracellular delivery than other PTDs. It has been demonstrated that fusion peptides containing the Tat PTD enter the central nervous system after systemic administration. Our previous study has shown that i.p. injected Tat-PSD-95 PDZ2 expresses in the central nervous system and significantly disrupts PDZ domain-mediated protein interactions between PSD-95 and N-methyl-D-aspartate receptor subunit NR2A/2B, thereby alleviating chronic pain. Therefore, Tat-mediated intracellular delivery can be used for systemic administration of analgesics in pain management.