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Significance Endothelial barriers are essential components of blood vessels and particularly important in brain and retina, which are protected by barriers so efficient that almost all metabolites have to be actively transported across them. We provide evidence that short peptides containing a motif rich in amino acids with aromatic and positively charged side chains target specifically blood vessels of the brain but not of other tissues. Using electron microscopy, phage could be visualized bound to the endothelial junction of these vessels, demonstrating how these two techniques can be combined to identify a supramolecular phage target in vivo. Surprisingly, this peptide motif does not bind to vessels in the retina, implying a previously unknown molecular difference between these endothelial junctions.

A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina