Drug Trafficking

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Science  01 Nov 2002:
Vol. 298, Issue 5595, pp. 925
DOI: 10.1126/science.298.5595.925b

In order to gain access to intracellular targets, drugs must be polar enough to dissolve in the bloodstream but nonpolar enough to travel across cellular boundaries. One way to overcome these limitations is to ship drugs on biological transporters, such as the viral transcription activator protein (Tat), whose critical permeability motif is a highly basic stretch of amino acids. Wender et al. investigated whether the peptide (amide) backbone could be modified to improve transporter activity in cells as well as to enhance protease resistance. They find that oligocarbamates (in which a -CH2O- increases the spacing between the basic groups) are highly effective for cellular uptake. In a model study, they show that biotin, which does not normally cross the skin barrier, could be delivered into the skin of nude mice. — PDS

J. Am. Chem. Soc. 10.1021/ja0275109.

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