Peptidomimetic macrocycles

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 R1 and R2 are independently —H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, or heterocycloalkyl, unsubstituted or substituted with halo-;
• each R3 is independently hydrogen, alkyl, alkenyl, alkynyl, arylalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, cycloalkylalkyl, cycloaryl, or heterocycloaryl, optionally substituted with R5;
• each L is independently a macrocycle-forming linker of the formula -L1-L2-;
• each L1 and L2 is independently alkylene, alkenylene, alkynylene, heteroalkylene, cycloalkylene, heterocycloalkylene, cycloarylene, heterocycloarylene, or [—R4—K—R4—]n, each being optionally substituted with R5;
• each R4 is independently alkylene, alkenylene, alkynylene, heteroalkylene, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene;
• each K is independently O, S, SO, SO2, CO, CO2, or CONR3;
• each R5 is independently halogen, alkyl, —OR6, —N(R6)2, —SR6, —SOR6, —SO2R6, —CO2R6, a fluorescent moiety, a radioisotope or a therapeutic agent;
• each R6 is independently —H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkylalkyl, heterocycloalkyl, a fluorescent moiety, a radioisotope or a therapeutic agent;
• each R7 is independently —H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heterocycloalkyl, cycloaryl, or heterocycloaryl, optionally substituted with R5, or part of a cyclic structure with a D residue;
• each R8 is independently —H, alkyl, alkenyl, alkynyl, arylalkyl, cycloalkyl, heteroalkyl, cycloalkylalkyl, heterocycloalkyl, cycloaryl, or heterocycloaryl, optionally substituted with R5, 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.