Skiles J W, Fuchs V, Chow G, Skoog M
Department of Biochemistry, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877.
Res Commun Chem Pathol Pharmacol. 1990 Jun;68(3):365-74.
Several tripeptide trifluoromethyl ketones containing non-naturally occurring N-substituted glycine residues at the P2-position are effective human leukocyte elastase (HLE) inhibitors in vitro and possess IC50 values in the submicromolar range. Deletion of the amino acid at the P3-subsite region affords inactive compounds. The trifluoromethyl ketone derivative of valine is the preferred residue at the P1-position; whereas, the corresponding glycine or alpha, alpha-dimethyl glycine analogs result in inactive compounds.
几种在P2位含有非天然存在的N-取代甘氨酸残基的三肽三氟甲基酮在体外是有效的人白细胞弹性蛋白酶（HLE）抑制剂，并且在亚微摩尔范围内具有IC50值。P3亚位点区域氨基酸的缺失会产生无活性的化合物。缬氨酸的三氟甲基酮衍生物是P1位的优选残基；而相应的甘氨酸或α,α-二甲基甘氨酸类似物会产生无活性的化合物。
