Paradoxical downregulation of CXC chemokine receptor 4 induced by polyphemusin II-derived antagonists

Ryo Masuda, Shinya Oishi, Noriko Tanahara, Hiroaki Ohno, Akira Hirasawa, Gozoh Tsujimoto, Yoshiaki Yano, Katsumi Matsuzaki, Jean Marc Navenot, Stephen C. Peiper, Nobutaka Fujii

研究成果: Article

5 引用 (Scopus)

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
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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CXCR4 Receptors
Down-Regulation
Derivatives
Chemokine CXCL12
Ligands
Tropics
T-cells
Labeling
Peptides
Physiological Phenomena
polyphemusin II
Proteins
Membranes
Structure-Activity Relationship
G-Protein-Coupled Receptors
T140 peptide
HIV-1
HIV
Neoplasm Metastasis
T-Lymphocytes

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

Masuda, R, Oishi, S, Tanahara, N, Ohno, H, Hirasawa, A, Tsujimoto, G, Yano, Y, Matsuzaki, K, Navenot, JM, Peiper, SC & Fujii, N 2012, 'Paradoxical downregulation of CXC chemokine receptor 4 induced by polyphemusin II-derived antagonists', Bioconjugate Chemistry, 巻. 23, 番号 6, pp. 1259-1265. https://doi.org/10.1021/bc300084h
Masuda, Ryo ; Oishi, Shinya ; Tanahara, Noriko ; Ohno, Hiroaki ; Hirasawa, Akira ; Tsujimoto, Gozoh ; Yano, Yoshiaki ; Matsuzaki, Katsumi ; Navenot, Jean Marc ; Peiper, Stephen C. ; Fujii, Nobutaka. / Paradoxical downregulation of CXC chemokine receptor 4 induced by polyphemusin II-derived antagonists. :: Bioconjugate Chemistry. 2012 ; 巻 23, 番号 6. pp. 1259-1265.
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AU - Yano, Yoshiaki

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AU - Fujii, Nobutaka

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