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

Abstract：

:Endothelial heterogeneity has important implications in health and disease. Molecular markers selectively expressed in the vasculature of different organs and tissues are currently being explored in targeted therapies with promising results in preclinical and clinical studies. Noteworthy is the role that combinatorial approaches such as phage display have had in identifying such markers by using phage as nanoparticles and surrogates for billions of different peptides, screening noninvasively the vascular lumen for binding sites. Here, we show that a new peptide motif that emerged from such combinatorial screening of the vasculature binds selectively to blood vessels in the brain in vivo but not to vessels in other organs. Peptides containing a conserved motif in which amino acids Phenylalanine-Arginine-Tryptophan (FRW) predominate could be visualized by transmission electron microscopy bound to the junctions between endothelial cells in all areas of the brain, including the optic nerve, but not in other barrier-containing tissues, such as intestines and testis. Remarkably, peptides containing the motif do not bind to vessels in the retina, implying an important molecular difference between these two vascular barriers. Furthermore, the peptide allows for in vivo imaging, demonstrating that new tools for studying and imaging the brain are likely to emerge from this motif.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Tang FHF,Staquicini FI,Teixeira AAR,Michaloski JS,Namiyama GM,Taniwaki NN,Setubal JC,da Silva AM,Sidman RL,Pasqualini R,Arap W,Giordano RJ

doi

10.1073/pnas.1809483116

subject

Has Abstract

pub_date

2019-02-05 00:00:00

pages

2300-2305

issue

6

eissn

0027-8424

issn

1091-6490

pii

1809483116

journal_volume

116

pub_type

杂志文章

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