Kruszynski M, Shealy D J, Leone A O, Heavner G A
Pharmaceutical Research, Centocor, Inc., 200 Great Valley Parkway, Malvern, PA 19355, USA.
Cytokine. 1999 Jan;11(1):37-44. doi: 10.1006/cyto.1998.0389.
Tumour necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine with pleiotropic activity that binds to two transmembrane receptors. Its role in mediating the inflammatory response to injury or infection has been well documented and it has been shown to be a causative factor in rheumatoid arthritis, inflammatory bowel disease and septic shock. Using synthetic peptide libraries composed exclusively of D-amino acids, two distinct hexapeptide families that block the binding of TNF-alpha to its receptors were identified. In the deconvolution of the library, activity increased from submillimolar to the low micromolar range with the most active compound having an IC50 of 0.33 microM. With the aid of biotinylated constructs of these hexapeptides it was possible to demonstrate that their antagonistic effect is due to specific binding to TNF-alpha and not to its receptor.
肿瘤坏死因子α（TNF-α）是一种具有多效性活性的促炎细胞因子，它可与两种跨膜受体结合。其在介导对损伤或感染的炎症反应中的作用已有充分记录，并且已证明它是类风湿性关节炎、炎症性肠病和败血症性休克的致病因素。使用仅由D-氨基酸组成的合成肽库，鉴定出了两个不同的六肽家族，它们可阻断TNF-α与其受体的结合。在肽库的反卷积过程中，活性从亚毫摩尔范围增加到低微摩尔范围，活性最高的化合物的IC50为0.33微摩尔。借助这些六肽的生物素化构建体，可以证明它们的拮抗作用是由于与TNF-α特异性结合，而不是与其受体结合。
