A head-to-tail macrocycle based on G1. A) Structures of G1, G1-Pro, and HT1-6. Side-chains shown in red are implicated in direct SH2 domain binding in the known structure-activity relationships of previous G1 analogs.[15b, 15d] Amino acids that differ from the parent peptide G1 are shown in blue. B) Competition assay data for G1, G1-Pro, HT1, HT2, and HT4. Data for HT3, HT5 and HT6 are similar to those for HT2 and HT4 and are shown in Figure S2. IC50 values reflect the curve fits shown.