Given the excellent result obtained with Py14 and with an eye towards facile labeling of IP + MPs for future protein-binding studies, we synthesized Py25 (Figure ), with a piperazine group bearing a free secondary amine, and asked if this compound was a suitable substrate. Gratifyingly, macrocyclization proceeded efficiently (Supplementary Figure ). The amine was readily modified with common labels such as biotin or carboxyfluorescein (Figure and Supplementary Figures ).