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Peptide-binding induced inhibition of chemokine cxcl12
Duan, Hongyang1,2,5; Zhu, Ling1,5; Peng, Jiaxi1,5; Yang, Mo1,5; Xie, Hanyi1,2,5; Lin, Yuchen1,5; Li, Wenzhe1,2,5; Liu, Changliang1,5; Li, Xiaojin3,4; Guo, Hua3,4
刊名Rsc advances
2017
卷号7期号:34页码:21298-21307
ISSN号2046-2069
DOI10.1039/c7ra01735a
通讯作者Xu, haiyan(xuhy@pumc.edu.cn) ; Wang, chen(wangch@nanoctr.cn) ; Yang, yanlian(yangyl@nanoctr.cn)
英文摘要The chemokine cxcl12, and its receptor cxcr4, have been recognized to be involved in various instances of cancer metastasis. the cxcl12/cxcr4 axis has emerged as a potential target for cancer therapy. here, we demonstrate a designed peptide (w4) targeting cxcl12 with high binding affinity, and describe its significant inhibitory effect on the cxcl12/cxcr4 axis. we show that w4 has comparable binding affinity (kd = 5.7 x 10(-8) m) to that of the antibody of cxcl12 (k-d = 3.0 x 10(-9) m) using the surface plasma resonance (spr) technique. upon introduction of w4, the circular dichroism (cd) spectra show that the alpha-helical structure of cxcl12 gradually transformed into a beta-sheet and random coil. these effects lead to the significant inhibitory effects on the cxcl12/cxcr4 axis using the cxcr4-positive breast cancer cell lines mcf-7 and mda-mb-231 and the leukemia cell lines hl-60 and u937 as models. the results show that w4 significantly inhibits cxcl12-induced cell migration of mcf-7, mda-mb-231, hl-60 and u937 even to 20.0% when the mole ratio is 1 : 1, completely abolishing the effect of cxcl12. these effects may provide evidence of the modulating ligand-receptor interactions of peptides as antiligand molecules that differ from the traditional receptor antagonists leading to therapeutic agents.
WOS关键词EPITHELIAL-MESENCHYMAL TRANSITION ; STROMAL-DERIVED FACTOR-1-ALPHA ; BREAST-CANCER METASTASIS ; LEUKEMIA B-CELLS ; CXCR4 ANTAGONISTS ; RECEPTOR CXCR4 ; TUMOR-CELLS ; IN-VITRO ; MIGRATION ; ACTIVATION
WOS研究方向Chemistry
WOS类目Chemistry, Multidisciplinary
语种英语
出版者ROYAL SOC CHEMISTRY
WOS记录号WOS:000399722300068
内容类型期刊论文
URI标识http://www.corc.org.cn/handle/1471x/2177191
专题高能物理研究所
通讯作者Xu, Haiyan; Wang, Chen; Yang, Yanlian
作者单位1.Natl Ctr Nanosci & Technol, CAS Ctr Excellence Nanosci, CAS Key Lab Standardizat & Measurement Nanotechno, CAS Key Lab Biol Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China
2.Peking Univ, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China
3.Chinese Acad Med Sci, Inst Basic Med Sci, Beijing 100005, Peoples R China
4.Peking Union Med Coll, Beijing 100005, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
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GB/T 7714
Duan, Hongyang,Zhu, Ling,Peng, Jiaxi,et al. Peptide-binding induced inhibition of chemokine cxcl12[J]. Rsc advances,2017,7(34):21298-21307.
APA Duan, Hongyang.,Zhu, Ling.,Peng, Jiaxi.,Yang, Mo.,Xie, Hanyi.,...&Yang, Yanlian.(2017).Peptide-binding induced inhibition of chemokine cxcl12.Rsc advances,7(34),21298-21307.
MLA Duan, Hongyang,et al."Peptide-binding induced inhibition of chemokine cxcl12".Rsc advances 7.34(2017):21298-21307.
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