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

Alan Ho, Steven R. Schwarze, Sarah J. Mermelstein, Gabriel Waksman, Steven F. Dowdy

Research output: Contribution to journalArticlepeer-review

376 Scopus citations

Abstract

The protein transduction domain (PTD) embedded in the HIV TAT protein (amino acids 47-57) has been shown to successfully mediate the introduction of heterologous peptldes and proteins in excess of Mr100,000 into mammalian cells in vitro and in vivo. We report here that the modeled structure of the TAT PTD is a strong amphipathic helix. On the basis of this information, we synthesized a series of synthetic PTDs that strengthen the α-helical content and optimize the placement of arginine residues. Several PTD peptides possessed significantly enhanced protein transduction potential compared with TAT in vitro and in vivo. These optimized PTDs have the potential to deliver both existing and novel anticancer therapeutics.

Original languageEnglish
Pages (from-to)474-477
Number of pages4
JournalCancer Research
Volume61
Issue number2
StatePublished - Jan 15 2001

Funding

FundersFunder number
National Institute of General Medical SciencesR01GM054033

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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