Abstract
The molecular diversity of receptors in human blood vessels remains largely unexplored. We developed a selection method in which peptides that home to specific vascular beds are identified after administration of a peptide library. Here we report the first in vivo screening of a peptide library in a patient. We surveyed 47,160 motifs that localized to different organs. This large-scale screening indicates that the tissue distribution of circulating peptides is nonrandom. High-throughput analysis of the motifs revealed similarities to ligands for differentially expressed cell-surface proteins, and a candidate ligand–receptor pair was validated. These data represent a step toward the construction of a molecular map of human vasculature and may have broad implications for the development of targeted therapies.
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Acknowledgements
We thank R.C. Bast, Jr., R.R. Brentani, W.K. Cavenee, A.C. von Eschenbach, I.J. Fidler, W.K. Hong, D.M. McDonald, J. Mendelsohn and L.A. Zwelling for comments on the manuscript; W.D. Heston for sharing unpublished data; C.L. Cavazos, P.Y. Dieringer, R.G. Nikolova, C.A. Perez, B.H. Restel, C.P. Soto and X. Wang for technical assistance. This work was funded in part by grants from NIH (CA90270 and CA8297601 to R.P., CA90270 and CA9081001 to W.A.) and awards from the Gilson–Longenbaugh Foundation and CaP CURE (to R.P. and W.A.). M.G.K., J.L. and P.J.M. received support from the Susan G. Komen Breast Cancer Foundation, R.J.G. from FAPESP (Brazil), M.C.V. from the Department of Defense, L.C. from the NCCRA and E.K. from the Academy of Finland.
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The University of Texas and W. Arap and R. Pasqualini have equity in NTTX Biotechnology, which is subject to certain restrictions under university policy. The terms of these arrangements are being managed by the university in accordance with its conflict-of-interest policies.
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Arap, W., Kolonin, M., Trepel, M. et al. Steps toward mapping the human vasculature by phage display. Nat Med 8, 121–127 (2002). https://doi.org/10.1038/nm0202-121
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DOI: https://doi.org/10.1038/nm0202-121
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