Steps toward mapping the human vasculature by phage display.

Department of Genito-Urinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
Nature Medicine (Impact Factor: 28.05). 03/2002; 8(2):121-7. DOI: 10.1038/nm0202-121
Source: PubMed

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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Available from: Ricardo J Giordano, Jul 30, 2015
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    • "For example , antibody and subfractionation strategies have been used to generate monoclonal antibodies that specifically target the caveolae in one vascular bed or another (McIntosh et al. 2002). Others have used phage display peptide libraries to select for peptides that home to specific vascular beds in vivo (Pasqualini and Ruoslahti 1996; Arap et al. 2002b). These latter studies have uncovered a vascular address system that allows for site-specific targeting of biologically active compounds, for example, to the endothelial lining of tumor blood vessels (Arap et al. 1998, 2002a). "
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    • "Resistin Is the ASC Interactor of DDCN We set out to investigate the biological interaction behind the WAT7-DDCN binding. Our previous studies have shown that peptides tend to recognize cell surface receptors through mimicking receptor-binding domains of the biological ligands for these receptors (Arap et al., 2002; Kolonin et al., 2006a, 2006b). In order to identify the biological ligand of DDCN, we raised antibodies against WAT7, which we expected to recognize the binding epitope of a mouse protein mimicked by WAT7. Figure 6A demonstrates that the generated WAT7 antibodies have high specificity for WAT7 and do not recognize any of the other ASC-homing peptides isolated in the screen. "
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    • "It has recently been demonstrated that phages expressing the amino acid sequence Asp-Gly-Arg (NGR) can bind CD13 (Pasqualini and Ruoslahti 1996; Pasqualini et al. 2000; Arap et al. 2002). Different CD13 forms are expressed within tumor vessels, normal epithelia, and myeloid cells (Curnis, et al. 2002), providing support for varying ligand specificities. "
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