title: Phage display selection of peptides that home to atherosclerotic plaques: IL-4 receptor as a candidate target in atherosclerosis.
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 vivo 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.
authors.affiliation: Department of Biochemistry and Cell Biology, Cell & Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Hong
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Wonjung
authors.initials: W
authors.lastname: Kwak
authors.forename: Jeongsoo
authors.initials: J
authors.lastname: Yoo
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Na
authors.forename: In Seop
authors.initials: IS
authors.lastname: So
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kwon
authors.forename: Heon-Sik
authors.initials: HS
authors.lastname: Park
authors.forename: Seung
authors.initials: S
authors.lastname: Huh
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
authors.forename: Ick-Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.forename: Byung-Heon
authors.initials: BH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D001345:Autoradiography; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009842:Oligopeptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019151:Peptide Library; D011485:Protein Binding / Q000235:genetics; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D019151:Peptide Library; D019948:Receptors, Interleukin-4; D011973:Receptors, LDL