Phage display selection of peptides that home to atherosclerotic plaques

IL-4 receptor as a candidate target in atherosclerosis

Hai Yan Hong, Hwa Young Lee, Wonjung Kwak, Jeongsoo Yoo, Moon Hee Na, In Seop So, Tae Hwan Kwon, Heon Sik Park, Seung Huh, Goo Taeg Oh, Ick Chan Kwon, In-San Kim, Byung Heon Lee

Research output: Contribution to journalArticle

58 Citations (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.

Original languageEnglish
Pages (from-to)2003-2014
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Volume12
Issue number5B
DOIs
Publication statusPublished - 2008 Oct 1
Externally publishedYes

Fingerprint

Interleukin-4 Receptors
Atherosclerotic Plaques
Bacteriophages
Atherosclerosis
Peptides
LDL Receptors
Interleukin Receptors
Peptide Library
Molecular Imaging
Fluorescein
Radioisotopes
Interleukin-4
Pharmaceutical Preparations
Smooth Muscle Myocytes
Cultured Cells

Keywords

  • Atherosclerotic plaque
  • Homing peptide
  • IL-4 receptor
  • LDL receptor
  • Phage display

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Phage display selection of peptides that home to atherosclerotic plaques : IL-4 receptor as a candidate target in atherosclerosis. / Hong, Hai Yan; Lee, Hwa Young; Kwak, Wonjung; Yoo, Jeongsoo; Na, Moon Hee; So, In Seop; Kwon, Tae Hwan; Park, Heon Sik; Huh, Seung; Oh, Goo Taeg; Kwon, Ick Chan; Kim, In-San; Lee, Byung Heon.

In: Journal of Cellular and Molecular Medicine, Vol. 12, No. 5B, 01.10.2008, p. 2003-2014.

Research output: Contribution to journalArticle

Hong, Hai Yan ; Lee, Hwa Young ; Kwak, Wonjung ; Yoo, Jeongsoo ; Na, Moon Hee ; So, In Seop ; Kwon, Tae Hwan ; Park, Heon Sik ; Huh, Seung ; Oh, Goo Taeg ; Kwon, Ick Chan ; Kim, In-San ; Lee, Byung Heon. / Phage display selection of peptides that home to atherosclerotic plaques : IL-4 receptor as a candidate target in atherosclerosis. In: Journal of Cellular and Molecular Medicine. 2008 ; Vol. 12, No. 5B. pp. 2003-2014.
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T2 - IL-4 receptor as a candidate target in atherosclerosis

AU - Hong, Hai Yan

AU - Lee, Hwa Young

AU - Kwak, Wonjung

AU - Yoo, Jeongsoo

AU - Na, Moon Hee

AU - So, In Seop

AU - Kwon, Tae Hwan

AU - Park, Heon Sik

AU - Huh, Seung

AU - Oh, Goo Taeg

AU - Kwon, Ick Chan

AU - Kim, In-San

AU - Lee, Byung Heon

PY - 2008/10/1

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N2 - 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.

AB - 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.

KW - Atherosclerotic plaque

KW - Homing peptide

KW - IL-4 receptor

KW - LDL receptor

KW - Phage display

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