Selectivity studies. The breadth of tolerated residues and the cyclic peptide variability (3-7 residues, 16-26 atom-containing macrocycles) accessible using a TAD-based cyclization strategy is showcased by the 20 examples of Tyr-linked peptides (16) in Figure . We were interested in expanding the scope of this strategy with regards to macrocycle size, location of Tyr (i.e., embedded vs. terminal), and site-selectivity when two Tyr residues are incorporated. Remarkably, 11-mer 14u is readily converted into cyclic peptide 16u in 21% isolated yield, despite the larger, 38-atomcontaining ring size and presence of potentially reactive Ser, Arg, and His residue side chain functionality (Figure ). This example demonstrates the potential utility of our approach for generating cyclic peptides from longer sequences that bear diverse residue side chain functionalities. Due to the therapeutic potential of lariat peptides, which can exhibit improved cell permeability relative to acyclic and head-to-tail macrocyclic variants, we evaluated the cyclization of 14v to demonstrate access to lariat-type peptide 16v that bears a Tyr residue at an embedded position (Figure ). Consistent with previous cases, 16v was efficiently formed in 45% isolated yield, indicating this strategy can be used to access peptides with diverse structures, including lariat-type peptides.