Patent ID: 7960506

Claim:
A peptidomimetic macrocycle of Formula (I): 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, an amino acid comprising one or more additional methylene groups between the amino and carboxyl group, an amino acid comprising an amino group which is a secondary or tertiary amine, an amino acid comprising a carboxy group replaced by an ester, [—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, cycloalkyl, heterocycloalkyl, cycloalkylalkyl, cycloaryl, or heterocycloaryl, unsubstituted or substituted with R 5 ; L 1 , L 2 , L 3 and L 4 are independently alkylene, alkenylene, alkynylene, heteroalkylene, heterocycloalkylene, or [—R 4 —K—R 4 —]n, each being unsubstituted or substituted with R 5 ; K is O, S, SO, SO 2 , CO, CO 2 , or CONR 3 ; each R 4 is alkylene, alkenylene, alkynylene, heteroalkylene, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene; 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 label, a radioisotope or a therapeutic agent; each R 6 is independently —H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkylalkyl, heterocycloalkyl, a fluorescent label, 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; n is an integer from 1-5; x+y+z is at least 3; and wherein the peptidomimetic macrocycle comprises an alpha-helix, wherein a secondary structure of the peptidomimetic macrocycle is more stable than a corresponding secondary structure of a corresponding non-macrocyclic polypeptide, and wherein the non-macrocyclic polypeptide lacks [-L 2 -].