Peptoid Mimics of HIV-Tat Protein

Alternatively, one interesting drug delivery technique exploits the active transport of certain naturally-occurring and relatively small biomacromolecules across the cellular membrane. For instance, the nuclear transcription activator protein (Tat) from HIV type 1 (HlV-1) is a 101-amino acid protein that must interact with a 59-base RNA stem-loop structure, called the traus-activation region (Tar) at the 5 end of all nascent HlV-1 mRNA molecules, in order for the vims to replicate. HIV-Tat is actively transported across the cell membrane, and localizes to the nucleus [28]. It has been found that the arginine-rich Tar-binding region of the Tat protein, residues 49-57 (Tat+9 57), is primarily responsible for this translocation activity [29]. 

Recently, there has been significant interest in peptidomimetic forms of Tat49 57, not only because of its membrane translocation activity, but as a means of treating HIV infection [1]. Several peptoids, similar in sequence to Tat49 57, have been synthesized with the intention of preventing the HlV-Tat/Tar interaction, and thus preventing HIV replication [24, 25, 30, 31]. However, only recently has this class of peptoids been applied to membrane translocation and dmg delivery applications. 

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