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

肽基-脯氨酰异构酶，Pin1，是一种催化磷酸-丝氨酸-Pro和磷酸-苏氨酸-Pro酰胺键异构化反应的酶。我计划开发基于含有硫酰胺的多肽的Pin1酶抑制剂。与多肽中的正常脯氨酰胺键相比，脯氨酸硫酰胺具有更大的异构化转动能。Pin1底物的硫代酰胺衍生物有望减缓Pin1的反应。我合成了硫代酰胺版本的Pin1底物多肽衍生物，并评价了其对Pin1酶的抑制活性。与活性部位的简单底物竞争相比，合成的硫代酰胺对Pin1具有更大的抑制活性。

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.