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

Fenny H.F. Tang, Fernanda I. Staquicini, André A.R. Teixeira, Jussara S. Michaloski, Gislene M. Namiyama, Noemi N. Taniwaki, João C. Setubal, Aline M. Da Silva, Richard L. Sidman, Renata Pasqualini, Wadih Arap, Ricardo J. Giordano

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2300-2305
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number6
DOIs
StatePublished - Feb 5 2019

Fingerprint

Blood Vessels
Retina
Ligands
Peptides
Brain
Bacteriophages
Optic Nerve
Phenylalanine
Transmission Electron Microscopy
Neuroimaging
Tryptophan
Nanoparticles
Intestines
Arginine
Testis
Endothelial Cells
Binding Sites
Amino Acids
Health
Therapeutics

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Blood-brain barrier
  • Blood-retina barrier
  • Brain endothelial cells
  • Peptide
  • Phage display

Cite this

Tang, F. H. F., Staquicini, F. I., Teixeira, A. A. R., Michaloski, J. S., Namiyama, G. M., Taniwaki, N. N., ... Giordano, R. J. (2019). A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina. Proceedings of the National Academy of Sciences of the United States of America, 116(6), 2300-2305. https://doi.org/10.1073/pnas.1809483116
Tang, Fenny H.F. ; Staquicini, Fernanda I. ; Teixeira, André A.R. ; Michaloski, Jussara S. ; Namiyama, Gislene M. ; Taniwaki, Noemi N. ; Setubal, João C. ; Da Silva, Aline M. ; Sidman, Richard L. ; Pasqualini, Renata ; Arap, Wadih ; Giordano, Ricardo J. / A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 6. pp. 2300-2305.
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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 2019, 'A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 6, pp. 2300-2305. https://doi.org/10.1073/pnas.1809483116

A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina. / Tang, Fenny H.F.; Staquicini, Fernanda I.; Teixeira, André A.R.; Michaloski, Jussara S.; Namiyama, Gislene M.; Taniwaki, Noemi N.; Setubal, João C.; Da Silva, Aline M.; Sidman, Richard L.; Pasqualini, Renata; Arap, Wadih; Giordano, Ricardo J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 6, 05.02.2019, p. 2300-2305.

Research output: Contribution to journalArticle

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T1 - A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina

AU - Tang, Fenny H.F.

AU - Staquicini, Fernanda I.

AU - Teixeira, André A.R.

AU - Michaloski, Jussara S.

AU - Namiyama, Gislene M.

AU - Taniwaki, Noemi N.

AU - Setubal, João C.

AU - Da Silva, Aline M.

AU - Sidman, Richard L.

AU - Pasqualini, Renata

AU - Arap, Wadih

AU - Giordano, Ricardo J.

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KW - Blood-brain barrier

KW - Blood-retina barrier

KW - Brain endothelial cells

KW - Peptide

KW - Phage display

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