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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
오구택scopus
Issue Date
2008
Journal Title
Journal of Cellular and Molecular Medicine
ISSN
1582-1838JCR Link
Citation
vol. 12, no. 5B, pp. 2003 - 2014
Indexed
SCIE; SCOPUS WOS scopus
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
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자연과학대학 > 생명과학전공 > Journal papers
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