Martens C L, Cwirla S E, Lee R Y, Whitehorn E, Chen E Y, Bakker A, Martin E L, Wagstrom C, Gopalan P, Smith C W
Affymax Research Institute, Palo Alto, California 94304, USA.
J Biol Chem. 1995 Sep 8;270(36):21129-36. doi: 10.1074/jbc.270.36.21129.
E-selectin is an inducible cell adhesion molecule which mediates rolling of neutrophils on the endothelium, an early event in the development of an inflammatory response. Inhibition of selectin-mediated rolling is a possible means for controlling inflammation-induced diseases, and several classes of compounds have been tested for this use. We describe here the use of recombinant peptide library screening for identification and optimization of novel ligands which bind to E-selectin. Several of these peptides bind with Kd values in the low nanomolar range and block E-selectin-mediated adhesion of neutrophils in static and flow-cell assays. Administration of the peptide to mice undergoing an acute inflammatory response reduced the extent of neutrophil transmigration to the site of inflammation, demonstrating the utility of this compound as a potential therapeutic. The identification of a peptide ligand for E-selectin suggests that the complete natural ligand for this adhesion molecule may include protein as well as carbohydrate moieties.
E-选择素是一种可诱导的细胞粘附分子，它介导中性粒细胞在内皮上滚动，这是炎症反应发展过程中的早期事件。抑制选择素介导的滚动是控制炎症性疾病的一种可能手段，已经对几类化合物进行了这种用途的测试。我们在此描述了使用重组肽库筛选来鉴定和优化与E-选择素结合的新型配体。其中几种肽以低纳摩尔范围内的解离常数（Kd）值结合，并在静态和流动细胞测定中阻断E-选择素介导的中性粒细胞粘附。将该肽给予经历急性炎症反应的小鼠可减少中性粒细胞向炎症部位的迁移程度，证明了该化合物作为潜在治疗剂的效用。E-选择素肽配体的鉴定表明，这种粘附分子的完整天然配体可能包括蛋白质以及碳水化合物部分。
