Given the high level of efficiency and broad scope of the IP + -forming macrocyclization reaction, we examined if this chemistry is suitable for the synthesis of MP libraries. Specifically, it was of interest to determine if the entire process could be miniaturized so as to be carried out on a small amount of TentaGel resin in the wells of a microtiter filter plate, which is the most convenient format for the creation of combinatorial libraries, including DNA-encoded libraries (DELs). To evaluate this issue, 20 different peptides, including eight tetrapeptides, four pentapeptides and four hexapeptides, were synthesized on Finally, three equivalents of a P2CA were added to each well to create the IP+-linked macrocycle. This protocol was carried out for five identical plates but in each case a different P2CA unit was added at the end. After incubation and washing, the material was released from the beads and completely deprotected using TFA. The products were analyzed by LC-MS.