Loetscher P, Gong J H, Dewald B, Baggiolini M, Clark-Lewis I
Theodor-Kocher Institute, University of Bern, CH 3000 Bern, Switzerland.
J Biol Chem. 1998 Aug 28;273(35):22279-83. doi: 10.1074/jbc.273.35.22279.
Peptides corresponding to the N-terminal 9 residues of stromal cell-derived factor-1 (SDF-1) have SDF-1 activity. SDF-1, 1-8, 1-9, 1-9 dimer, and 1-17 induced intracellular calcium and chemotaxis in T lymphocytes and CEM cells and bound to CXC chemokine receptor 4 (CXCR4). The peptides had similar activities to SDF-1 but were less potent. Whereas native SDF-1 had half-maximal chemoattractant activity at 5 nM, the 1-9 dimer required 500 nM and was therefore 100-fold less potent. The 1-17 and a 1-9 monomer analog were 4- and 36-fold, respectively, less potent than the 1-9 dimer. Both the chemotactic and calcium response of the 1-9 dimer was inhibited by an antibody to CXCR4. The basis for the enhanced activity of the dimer form of SDF-1, 1-9 is uncertain, but it could involve an additional fortuitous binding site on the 1-9 peptide in addition to the normal SDF-1, 1-9 site. A 1-9 analog, 1-9[P2G] dimer, was found to be a CXCR4 antagonist. Overall this study shows that the N-terminal peptides are CXCR4 agonists or antagonists, and these could be leads for high affinity ligands.
与基质细胞衍生因子-1（SDF-1）N端9个残基对应的肽段具有SDF-1活性。SDF-1、1-8、1-9、1-9二聚体和1-17可诱导T淋巴细胞和CEM细胞内的钙离子流动及趋化作用，并与CXC趋化因子受体4（CXCR4）结合。这些肽段具有与SDF-1相似的活性，但效力较低。天然SDF-1在5 nM时具有半数最大趋化活性，而1-9二聚体则需要500 nM，因此效力低100倍。1-17和1-9单体类似物的效力分别比1-9二聚体低4倍和36倍。1-9二聚体的趋化和钙离子反应均被抗CXCR4抗体抑制。SDF-1 1-9二聚体形式活性增强的原因尚不确定，但除了正常的SDF-1 1-9位点外，可能还涉及1-9肽段上一个额外的偶然结合位点。一种1-9类似物1-9[P2G]二聚体被发现是一种CXCR4拮抗剂。总体而言，这项研究表明N端肽段是CXCR4激动剂或拮抗剂，这些可能是高亲和力配体的先导物。
