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  • Title: Tuning the transport properties of HIV-1 Tat arginine-rich motif in living cells.
    Author: Cardarelli F, Serresi M, Bizzarri R, Beltram F.
    Journal: Traffic; 2008 Apr; 9(4):528-39. PubMed ID: 18182009.
    Abstract:
    A large body of work is currently devoted to the rational design of new molecular carriers for the controlled delivery of cargoes (e.g. proteins or nucleic acids) to relevant subcellular domains, particularly the nucleus. In this article, we show that rational mutagenesis of the human immunodeficiency virus type 1 Tat-derived peptide (YGRKKRRQRRR) affords variants with finely tuned intercompartmental dynamics and controllable transport mechanisms. Our findings are made possible by the demonstration that the Tat peptide possesses two competing functionalities capable of active nuclear targeting and additional binding to intracellular moieties. By altering the competition between these two functions, we show how to control cargo localization of Tat peptide chimeras. Our investigation provides a unified, coherent description of previous conflicting in vivo and in vitro results and lets the true nature of the Tat peptide emerge.
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