We turned to peptide swap experiments to test whether reciprocal exchanges of the C-terminal residues of minimal ECD complex-binding CGRP and AM peptides (Moad and Pioszak, 2013) could exchange their receptor selectivity. In the competition AlphaScreen assay, CGRP(27-37)NH2 [F37Y] retained the ability to bind the CGRP receptor ECD complex (Figure 6E) and did not gain AM-like affinity for the AM1 receptor ECD complex (Figure 6H). CGRPmut [F37Y] retained CGRP receptor ECD complex binding (Figure 6F) and gained the ability to bind the AM1 receptor ECD complex as strongly as AM (Figure 6I). AM(37-52)NH2 [Y52F] exhibited significantly diminished binding to the AM1 receptor ECD complex (Figure 6J) but did not gain increased affinity for the CGRP receptor ECD complex (Figure 6G). These results suggested that the RAMP2 E101-AM Y52 hydrogen bond is a key contributor to AM1 receptor selectivity, whereas Phe as the peptide C-terminal residue is insufficient to confer CGRP receptor selectivity.