抄録
CXC chemokine receptor 4 (CXCR4) is a G protein-coupled receptor implicated in cell entry of T-cell line-tropic HIV-1 strains. CXCR4 and its ligand stromal cell derived factor-1 (SDF-1)/CXCL12 play pivotal parts in many physiological processes and pathogenetic conditions (e.g., immune cell-homing and cancer metastasis). We previously developed the potent CXCR4 antagonist T140 from structure-activity relationship studies of the antimicrobial peptide polyphemusin II. T140 and its derivatives have been exploited in biological and biomedical studies for the SDF-1/CXCR4 axis. We investigated receptor localization upon ligand stimulation using fluorescent SDF-1 and T140 derivatives as well as a specific labeling technique for cellular-membrane CXCR4. Fluorescent T140 derivatives induced translocation of CXCR4 into the perinuclear region as observed by treatment with fluorescent SDF-1. T140 derivative-mediated internalization of CXCR4 was also monitored by the coiled-coil tag-probe system. These findings demonstrated that the CXCR4 antagonistic activity and anti-HIV activity of T140 derivatives were derived (at least in part) from antagonist-mediated receptor internalization. (Figure Presented)
| 元の言語 | English |
|---|---|
| ページ（範囲） | 1259-1265 |
| ページ数 | 7 |
| ジャーナル | Bioconjugate Chemistry |
| 巻 | 23 |
| 発行部数 | 6 |
| DOI | |
| 出版物ステータス | Published - 2012 6 20 |
| 外部発表 | Yes |
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ASJC Scopus subject areas
- Biotechnology
- Bioengineering
- Organic Chemistry
- Pharmaceutical Science
- Biomedical Engineering
- Pharmacology
これを引用
Paradoxical downregulation of CXC chemokine receptor 4 induced by polyphemusin II-derived antagonists. / Masuda, Ryo; Oishi, Shinya; Tanahara, Noriko; Ohno, Hiroaki; Hirasawa, Akira; Tsujimoto, Gozoh; Yano, Yoshiaki; Matsuzaki, Katsumi; Navenot, Jean Marc; Peiper, Stephen C.; Fujii, Nobutaka.
：: Bioconjugate Chemistry, 巻 23, 番号 6, 20.06.2012, p. 1259-1265.研究成果: Article
}
TY - JOUR
T1 - Paradoxical downregulation of CXC chemokine receptor 4 induced by polyphemusin II-derived antagonists
AU - Masuda, Ryo
AU - Oishi, Shinya
AU - Tanahara, Noriko
AU - Ohno, Hiroaki
AU - Hirasawa, Akira
AU - Tsujimoto, Gozoh
AU - Yano, Yoshiaki
AU - Matsuzaki, Katsumi
AU - Navenot, Jean Marc
AU - Peiper, Stephen C.
AU - Fujii, Nobutaka
PY - 2012/6/20
Y1 - 2012/6/20
N2 - CXC chemokine receptor 4 (CXCR4) is a G protein-coupled receptor implicated in cell entry of T-cell line-tropic HIV-1 strains. CXCR4 and its ligand stromal cell derived factor-1 (SDF-1)/CXCL12 play pivotal parts in many physiological processes and pathogenetic conditions (e.g., immune cell-homing and cancer metastasis). We previously developed the potent CXCR4 antagonist T140 from structure-activity relationship studies of the antimicrobial peptide polyphemusin II. T140 and its derivatives have been exploited in biological and biomedical studies for the SDF-1/CXCR4 axis. We investigated receptor localization upon ligand stimulation using fluorescent SDF-1 and T140 derivatives as well as a specific labeling technique for cellular-membrane CXCR4. Fluorescent T140 derivatives induced translocation of CXCR4 into the perinuclear region as observed by treatment with fluorescent SDF-1. T140 derivative-mediated internalization of CXCR4 was also monitored by the coiled-coil tag-probe system. These findings demonstrated that the CXCR4 antagonistic activity and anti-HIV activity of T140 derivatives were derived (at least in part) from antagonist-mediated receptor internalization. (Figure Presented)
AB - CXC chemokine receptor 4 (CXCR4) is a G protein-coupled receptor implicated in cell entry of T-cell line-tropic HIV-1 strains. CXCR4 and its ligand stromal cell derived factor-1 (SDF-1)/CXCL12 play pivotal parts in many physiological processes and pathogenetic conditions (e.g., immune cell-homing and cancer metastasis). We previously developed the potent CXCR4 antagonist T140 from structure-activity relationship studies of the antimicrobial peptide polyphemusin II. T140 and its derivatives have been exploited in biological and biomedical studies for the SDF-1/CXCR4 axis. We investigated receptor localization upon ligand stimulation using fluorescent SDF-1 and T140 derivatives as well as a specific labeling technique for cellular-membrane CXCR4. Fluorescent T140 derivatives induced translocation of CXCR4 into the perinuclear region as observed by treatment with fluorescent SDF-1. T140 derivative-mediated internalization of CXCR4 was also monitored by the coiled-coil tag-probe system. These findings demonstrated that the CXCR4 antagonistic activity and anti-HIV activity of T140 derivatives were derived (at least in part) from antagonist-mediated receptor internalization. (Figure Presented)
UR - http://www.scopus.com/inward/record.url?scp=84862694677&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862694677&partnerID=8YFLogxK
U2 - 10.1021/bc300084h
DO - 10.1021/bc300084h
M3 - Article
C2 - 22486464
AN - SCOPUS:84862694677
VL - 23
SP - 1259
EP - 1265
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 6
ER -