Yoshimoto T, Tsuru D, Yamamoto N, Ikezawa R, Furukawa S
School of Pharmaceutical Sciences, Nagasaki University, Japan.
Agric Biol Chem. 1991 Jan;55(1):37-43.
Structural requirements of N-blocked L-proline derivatives as specific inhibitors for prolyl endopeptidase were investigated using a series of substrate analogs. Replacement of L-proline by its D-isomer remarkably reduced the inhibition. Introduction of a sulfur atom in proline and/or in the penultimate pyrrolidine rings significantly increased the inhibition, but the introduction of oxygen rather diminished the activity. A peptide linkage (acid-amide bond) between the proline and the pyrrolidine ring was also required to keep the inhibitory activity. A benzyloxycarbonyl group was most effective as an N-blocked component of the inhibitors.
使用一系列底物类似物研究了N-封端的L-脯氨酸衍生物作为脯氨酰内肽酶特异性抑制剂的结构要求。用其D-异构体取代L-脯氨酸可显著降低抑制作用。在脯氨酸和/或倒数第二个吡咯烷环中引入硫原子可显著提高抑制作用，但引入氧反而会降低活性。脯氨酸和吡咯烷环之间的肽键（酸-酰胺键）也是保持抑制活性所必需的。苄氧羰基作为抑制剂的N-封端成分最为有效。
