Development of peptidyl prolyl isomerase Pin1 inhibitors based on thioamide isomerization energy

肽基脯氨酸异构酶（Pin1）是一种催化磷酸丝氨酸-脯氨酸和磷酸苏氨酸-脯氨酸酰胺键异构化反应的酶。我计划开发基于含硫酰胺肽的Pin1酶抑制剂。与正常的脯氨酸酰胺键相比，脯氨酸硫酰胺键具有更大的异构化旋转能。Pin1底物的硫酰胺衍生物有望减缓Pin1的反应。合成了硫酰胺型Pin1底物肽衍生物，并评价了其对Pin1酶的抑制活性。合成的硫酰胺对Pin1的抑制活性比在活性位点竞争的简单底物更强。

Peptidyl prolyl isomerase, Pin1, is an enzyme that catalyzes isomerization reaction of phosopho-serine-proline and phospho-threonine-proline amide bond. I planned to develop inhibitors for Pin1 enzyme based on thioamide-containing peptides. Proline thioamide has larger rotation energy for isomerization in comparison with normal proline amide bonds in peptides. Thioamide derivatives of the substrate for Pin1 are expected to slow the reaction of Pin1. I synthesized thioamide version of Pin1 substrate peptide derivatives and evaluate its inhibitory activity for Pin1 enzyme. The synthesized thioamide showed larger inhibitory activity against Pin1 in comparison with the simple substrate competition at the active site.