Flexible Semi-synthesisof UFM1_1–82–Propargylamine by Aminolysiswith Valine–Propargylamine

We report a novel semi-synthetic strategy of UFM1_1–82–propargylamine by N–S acyl transfer to give UFM1_1–80R thioester and subsequent aminolysis with valine–propargylamine. The use of the valine–propargylamine molecule overcomes the inability of the valine site to efficiently undergo the N–S acyl transfer. This strategy benefits from the availability of raw materials for bulk expression, and the resulting probe shows high selectivity toward UFM1-specific proteases in buffers and cell lysates.