An α-helix containing peptidomimetic macrocycle, of Formula: wherein: each A, C, D, and E is independently a natural or non-natural amino acid; B is a natural or non-natural amino acid, amino acid analog, [-NH-L 4 -CO-], [-NH-L 4 -SO 2 -], or [-NH-L 4 -]; R 1 and R 2 are independently H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, or heterocycloalkyl, unsubstituted or substituted with halo; R 3 is hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, heteroalkyl, heterocycloalkyl, or cycloalkylalkyl, unsubstituted or substituted with R 5; L 1, L 2, L 3 and L 4 are independently alkylene, alkenylene, alkynylene, heteroalkylene, or heterocycloalkylene, each being unsubstituted or substituted with R 5; each R 5 is independently halogen, alkyl, -OR 6, -N(R 6) 2, -SR 6, -SOR 6, SO 2 R 6, -CO 2 R 6, a fluorescent moiety, a radioisotope or a therapeutic agent; each R 6 is independently H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkylalkyl, heterocycloalkyl, a fluorescent moiety, a radioisotope or a therapeutic agent; R 7 is H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heterocycloalkyl, cycloaryl, or heterocycloaryl, unsubstituted or substituted with R 5,or part of a cyclic structure with a D residue; R 8 is H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heterocycloalkyl, cycloaryl, or heterocycloaryl, unsubstituted or substituted with R 5, or part of a cyclic structure with an E residue; v is an integer from 1-1000; w is an integer from 1-1000; x is an integer from 0-10; y is an integer from 0-10; z is an integer from 0-10; and x+y+z is at least 3; the macrocycle-forming linker L 1 -S-L 2 -S-L 3 spans 1 turn, 2 turns, 3 turns, 4 turns, or 5 turns of the α-helix. each A, C, D, and E is independently a natural or non-natural amino acid; B is a natural or non-natural amino acid, amino acid analog, [-NH-L 4 -CO-], [-NH-L 4 -SO 2 -], or [-NH-L 4 -]; R 1 and R 2 are independently H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, or heterocycloalkyl, unsubstituted or substituted with halo; R 3 is hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, heteroalkyl, heterocycloalkyl, or cycloalkylalkyl, unsubstituted or substituted with R 5; L 1, L 2, L 3 and L 4 are independently alkylene, alkenylene, alkynylene, heteroalkylene, or heterocycloalkylene, each being unsubstituted or substituted with R 5; each R 5 is independently halogen, alkyl, -OR 6, -N(R 6) 2, -SR 6, -SOR 6, SO 2 R 6, -CO 2 R 6, a fluorescent moiety, a radioisotope or a therapeutic agent; each R 6 is independently H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkylalkyl, heterocycloalkyl, a fluorescent moiety, a radioisotope or a therapeutic agent; R 7 is H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heterocycloalkyl, cycloaryl, or heterocycloaryl, unsubstituted or substituted with R 5,or part of a cyclic structure with a D residue; R 8 is H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heterocycloalkyl, cycloaryl, or heterocycloaryl, unsubstituted or substituted with R 5, or part of a cyclic structure with an E residue; v is an integer from 1-1000; w is an integer from 1-1000; x is an integer from 0-10; y is an integer from 0-10; z is an integer from 0-10; and x+y+z is at least 3; the macrocycle-forming linker L 1 -S-L 2 -S-L 3 spans 1 turn, 2 turns, 3 turns, 4 turns, or 5 turns of the α-helix.