School of Chemical Sciences, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
J Enzyme Inhib Med Chem. 2010 Feb;25(1):1-12. doi: 10.3109/14756360902888184.
Cathepsins are known to have many important physiological roles and provide a viable target for inhibition. Fluorobenzoyl dipeptide derivatives were synthesized and tested for biological activity in an effort to find an efficient inhibitor of the cysteine protease cathepsin L. Thirty-six novel inhibitors (1-36) were synthesized from protected amino acids via the standard DCC/HOBt coupling protocol, containing a benzyl ester or a nitrile as an electrophilic warhead. The activity of the inhibitors was evaluated against cathepsin L and IC50 values calculated. Modification of both amino acids and terminal groups afforded compounds with single digit micromolar inhibition. Results utilizing the benzoyl-L-leucine-glycine nitrile backbone are comparable to that for the commercially available inhibitor 39.
组织蛋白酶已知具有许多重要的生理作用，并提供了一个可行的抑制靶标。合成了氟苯甲酰二肽衍生物，并对其生物活性进行了测试，以期找到一种有效的半胱氨酸蛋白酶组织蛋白酶 L 的抑制剂。通过标准的 DCC/HOBt 偶联方案，从保护氨基酸合成了 36 种新型抑制剂（1-36），其中包含苄酯或腈作为亲电弹头。评估了抑制剂对组织蛋白酶 L 的活性，并计算了 IC50 值。对氨基酸和末端基团的修饰提供了具有个位数微摩尔抑制作用的化合物。利用苯甲酰基-L-亮氨酸-甘氨酸腈骨架的结果与商业上可用的抑制剂 39 相当。
