Peptidomimetic macrocycles

1. A peptidomimetic macrocycle-comprising a crosslinker linking the α-positions of at least two amino acids, and an amino acid sequence that is at least 80% identical to the amino acid sequence NleDVN$TLL$LKVAibAQ (SEQ ID NO: 113) and, wherein the peptidomimetic macrocycle has a structure of Formula (I):

wherein:

each A, C, D, and E is independently a natural or non-natural amino acid;

each B is independently a natural or non-natural amino acid, amino acid analog, or

each R 1 and R 2 are independently —H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, or heterocycloalkyl, unsubstituted or substituted with halo-; each R 3 is independently hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, cycloalkylalkyl, cycloaryl, or heterocycloaryl, optionally substituted with R 5 ;

each L is independently a macrocycle-forming linker of the formula -L 1 -L 2 -;

each L 1 and L 2 is independently alkylene, alkenylene, alkynylene, heteroalkylene, cycloalkylene, heterocycloalkylene, cycloarylene, heterocycloarylene, or [—R 4 —K—R 4 —] n , each being optionally substituted with R 5 ;

each R 4 is independently alkylene, alkenylene, alkynylene, heteroalkylene, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene;

each K is independently O, S, SO, SO 2 , CO, CO 2 , or CONR 3 ;

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;

each R 7 is independently —H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heterocycloalkyl, cycloaryl, or heterocycloaryl, optionally substituted with R 5 , or part of a cyclic structure with a D residue;

each R 8 is independently —H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heterocycloalkyl, cycloaryl, or heterocycloaryl, optionally substituted with R 5 , or part of a cyclic structure with an E residue;

amino acids represented as $ are alpha-Me S5-pentenyl-alanine olefin amino acids;

each v and w are independently integers from 1-1000;

u is an integer from 1-10;

each x, y and z are independently integers from 0-10; and

each n is independently an integer from 1-5.

2. The peptidomimetic macrocycle of claim 1 , wherein the amino acid sequence of the peptidomimetic macrocycle is at least about 90% identical to the amino acids sequence NleDVN$TLL$LKVAibAQ (SEQ ID NO: 113).

3. The peptidomimetic macrocycle of claim 1 , wherein the peptidomimetic macrocycle comprises a helix.

4. The peptidomimetic macrocycle of claim 1 , wherein the peptidomimetic macrocycle comprises a 3 10 helix.

5. The peptidomimetic macrocycle of claim 1 , wherein the peptidomimetic macrocycle comprises an α,α-disubstituted amino acid.

6. The peptidomimetic macrocycle of claim 1 , wherein x+y+z=6.

7. The peptidomimetic macrocycle of claim 1 , wherein the peptidomimetic macrocycle comprises an alpha helix.

8. The peptidomimetic macrocycle of claim 1 , wherein R 1 is alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, or heterocycloalkyl, unsubstituted or substituted with halo-.

9. The peptidomimetic macrocycle of claim 1 , wherein R 1 and R 2 are independently alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, or heterocycloalkyl, unsubstituted or substituted with halo-.