Structure-Activity Relationship Study of Cyclic Pentapeptide Ligands for Atypical Chemokine Receptor 3 (ACKR3)

被引:3
|
作者
Sekiguchi, Haruka [1 ]
Kuroyanagi, Tomoko [1 ]
Rhainds, David [2 ,3 ]
Kobayashi, Kazuya [4 ]
Kobayashi, Yuka [1 ]
Ohno, Hiroaki [1 ]
Heveker, Nikolaus [2 ,3 ]
Akaji, Kenichi [4 ]
Fujii, Nobutaka [1 ]
Oishi, Shinya [1 ]
机构
[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan
[2] Univ Montreal, Dept Biochim, Montreal, PQ H3T 1J4, Canada
[3] Univ Montreal, St Justine Hosp, Res Ctr, Montreal, PQ H3T 1C5, Canada
[4] Kyoto Pharmaceut Univ, Yamashina Ku, Kyoto 6078412, Japan
基金
加拿大健康研究院;
关键词
CXCR4/CXCR7/CXCL12; PATHWAY; CXCR4; ANTAGONISTS; PROSTATE-CANCER; MIGRATION; CXCL12/SDF-1; TC14012; GROWTH; CELLS; RDC1;
D O I
10.1021/acs.jmedchem.8b00336
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The atypical chemokine receptor 3 (ACKR3)/CXC chemokine receptor 7 (CXCR7) recognizes stromal cell derived factor 1 (SDF-1)/CXCL12 and is involved in a number of physiological and pathological processes. Here, we investigated the SAR of the component amino acids in an ACKR3-selective ligand, FC313 [cyclo(-D-Tyr-L-Arg-L-MeArgL-Nal(2)-L-Pro-)], for the development of highly active ACKR3 ligands. Notably, modification at the L-Pro position with toward ACKR3. a bulky hydrophobic side chain led to improved bioactivity toward ACKR3.
引用
收藏
页码:3745 / 3751
页数:7
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