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Phage display selection of peptides that home to atherosclerotic plaques: IL-4 receptor as a candidate target in atherosclerosis
- Title
- Phage display selection of peptides that home to atherosclerotic plaques: IL-4 receptor as a candidate target in atherosclerosis
- Authors
- Hong H.-Y.; Lee H.Y.; Kwak W.; Yoo J.; Na M.-H.; So I.S.; Kwon T.-H.; Park H.-S.; Huh S.; Oh G.T.; Kwon I.-C.; Kim I.-S.; Lee B.-H.
- Ewha Authors
- 오구택
- SCOPUS Author ID
- 오구택
- Issue Date
- 2008
- Journal Title
- Journal of Cellular and Molecular Medicine
- ISSN
- 1582-1838
- Citation
- Journal of Cellular and Molecular Medicine vol. 12, no. 5B, pp. 2003 - 2014
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Imaging or drug delivery tools for atherosclerosis based on the plaque biology are still insufficient. Here, we attempted to identify peptides that selectively home to atherosclerotic plaques using phage display. A phage library containing random peptides was ex viv screened for binding to human atheroma tissues. After three to four rounds of selection, the DNA inserts of phage clones wer sequenced. A peptide sequence, CRKRLDRNC, was the most frequently occurring one. Intravenously injected phage displaying the CRKRLDRNC peptide was observed to home to atherosclerotic aortic tissues of low-density lipoprotein receptor-deficient (Ldlr-/-) mice at higher levels than to normal aortic tissues of wild-type mice. Moreover, a fluorescein- or radioisotope-conjugated synthetic CRKRLDRNC peptide, but not a control peptide, homed in vivo to atherosclerotic plaques in Ldlr-/- mice, while homing of the peptide to other organs such as brain was minimal. The homing peptide co-localized with endothelial cells, macrophages and smooth muscle cells a mouse and human atherosclerotic plaques. Homology search revealed that the CRKRLDRNC peptide shares a motif of interleukin-receptor (IL-4) that is critical for binding to its receptor. The peptide indeed co-localized with IL-4 receptor (IL-4R) at atherosclerotic plaques. Moreover, the peptide bound to cultured cells expressing IL-4R on the cell surface and the binding was inhibited by the knock-down of IL-4R. These results show that the CRKRLDRNC peptide homes to atherosclerotic plaques through binding to IL-4R as its target and may be a useful tool for selective drug delivery and molecular imaging of atherosclerosis. © 2007 The Authors.
- DOI
- 10.1111/j.1582-4934.2008.00189.x
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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