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J Biol Chem, Vol. 274, Issue 17, 11593-11598, April 23, 1999
From the Cancer Research Center, The Burnham Institute,
La Jolla, California 92037
In vivo phage display is a powerful
method to study organ- and tissue-specific vascular addresses. Using
this approach, peptides capable of tissue-specific homing can be
identified by performing a selection for that trait in
vivo. We recently showed that the CGFECVRQCPERC (termed GFE-1)
peptide can selectively bind to mouse lung vasculature after an
intravenous injection. Our aim in the present study was to identify the
receptor for this lung-homing peptide. By using affinity
chromatography, we isolated a 55-kDa lung cell-surface protein that
selectively binds to the GFE-1 peptide. Protein sequencing established
the identity of the receptor as membrane dipeptidase (MDP), a
cell-surface zinc metalloprotease involved in the metabolism of
glutathione, leukotriene D4, and certain
-lactam
antibiotics. Phage particles displaying the GFE-1 peptide selectively
bind to COS-1 cells transfected with the murine MDP cDNA. Moreover,
the synthetic GFE-1 peptide could inhibit MDP activity. By establishing
MDP as the receptor for the GFE-1 peptide, our results suggest
potential applications for both MDP and the GFE-1 peptide in delivery
of compounds to the lungs. This work also demonstrates that
cell-surface proteases can be involved in tissue-specific homing.
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