Disclosed are peptidomimetic macrocycles comprising a helix, such as an alpha helix, and methods of using such macrocycles for the treatment of disease such as cancer. In other aspects, the peptidomimetic macrocycle comprises an α,α-disubstituted amino acid, or may comprise a crosslinker linking the α-positions of at least two amino acids or at least one of said two amino acids may be an α,α-disubstituted amino acid. Further included is the targeting of components of the Wnt signaling pathway such as the Tcf4-/3-catenin complex.
