Steps toward mapping the human vasculature by phage display
Steps toward mapping the human vasculature by phage display
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DOI：
10.1038/nm0202-121
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发表时间：
2002-02-01
期刊：
影响因子：
82.9
通讯作者：
Pasqualini, R
中科院分区：
文献类型：
--
作者：
Arap, W;Kolonin, MG;Pasqualini, R
人类血管中受体的分子多样性在很大程度上仍未被探索。我们开发了一种选择方法，其中在肽文库的施用后鉴定归巢至特定血管床的肽。在这里，我们报告的第一个在体内筛选的肽库的患者。我们调查了47,160个定位于不同器官的图案。这种大规模筛选表明循环肽的组织分布是非随机的。高通量分析的图案显示的相似性，差异表达的细胞表面蛋白的配体，和候选配体受体对进行了验证。这些数据代表了构建人类血管系统分子图谱的一个步骤，并可能对靶向治疗的发展产生广泛的影响。
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.