Dimeric peptides of the C-terminal region of CXCL14 function as CXCL12 inhibitors
Dimeric peptides of the C-terminal region of CXCL14 function as CXCL12 inhibitors
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CXCL14 C 末端区域的二聚肽充当 CXCL12 抑制剂
DOI：
10.1016/j.febslet.2013.10.017
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发表时间：
2013
期刊：
影响因子：
3.5
通讯作者：
and T. Hara
中科院分区：
文献类型：
--
作者：
K. Tanegashima;K. Tsuji;K. Su zuki;A. Shigenaga;A. Otaka;and T. Hara
我们最近报道CXCL14以高亲和力与CXCR4结合并抑制CXCL12介导的趋化性。在这里，我们发现 CXCL14 的 C 端 51-77 个氨基酸残基负责 CXCR4 结合。 CXCL14(51–77) 的二硫键二聚体肽与 CXCR4 结合，其亲和力与全长 CXCL14 相当，并表现出 CXCL12 抑制剂活性。 CXCR4 在与二聚体 CXCL14(51–77) 结合后被有效内化，从而在细胞表面被还原。 5 个氨基酸残基的取代结合使用肟接头进行二聚化增加了二聚体 CXCL14(51–77) 的溶解度和化学稳定性。
We recently reported that CXCL14 binds to CXCR4 with high affinity and inhibits CXCL12-mediated chemotaxis. Here we found that the C-terminal 51–77 amino acid residues of CXCL14 are responsible for CXCR4 binding. A disulfide dimer peptide of CXCL14(51–77) bound to CXCR4 with comparable affinity to full length CXCL14, and exhibited CXCL12 inhibitor activity. CXCR4 was efficiently internalized upon binding of dimeric CXCL14(51–77), thereby being reduced on the cell surface. Substitution of 5 amino acid residues in combination with the use of an oxime linker for dimerization increased the solubility and chemical stability of the dimeric CXCL14(51–77).