Selective mcl-1 binding peptides

Abstract

Provided herein are peptides that bind Mcl-1. Also provided are compositions containing these polypeptides and methods of using such peptides in the treatment of cancer that include administering to a subject one of the polypeptides.

1 . A compound comprising the amino acid sequence:
 1F 1G 2A 2B 2C 2D 2E 2F 2G 3A 3B 3C 3D 3E 3F 3G 4A 4B 4C 4D 4E 4F 4G 5A (SEQ ID NO: 1),
 wherein 1F is R or a conservative substitution or is missing; 1G is P or a conservative substitution or is missing; 2A is E or a conservative substitution or is missing; 2B is I or a conservative substitution; 2C is W or a conservative substitution; 2D is M or a conservative substitution, or norleucine (B); 2E is T or a conservative substitution, V or a conservative substitution, 2-aminoisobutyric acid (Aib); 2F is Q or a conservative substitution; 2G is G or a conservative substitution; 3A is L or a conservative substitution, F or a conservative substitution, pentafluoro phenylalanine, cyclohexyl alanine (Cha), or homo-cyclohexyl alanine (H-Cha); 3B is R or a conservative substitution, W or a conservative substitution, Q or a conservative substitution, D or a conservative substitution, Y or a conservative substitution, Aib, D-phenyl glycine, α,α methyl leucine, α,α methyl phenylalanine; 3C is R or a conservative substitution; 3D is L or a conservative substitution; 3E is G or a conservative substitution; 3F is D or a conservative substitution; 3G is E or a conservative substitution; 4A is I or a conservative substitution; 4B is N or a conservative substitution; 4C is A or a conservative substitution; 4D is Y or a conservative substitution; 4E is Y or a conservative substitution; 4F is A or a conservative substitution; 4G is R or a conservative substitution or is missing; 5A is R or a conservative or is missing; 
 provided that 2E, 3A, 3B, 4B and 4F are not T, L, R, N and A respectively, and wherein optionally, the side chains of two amino acids separated by 3 or 6 amino acids are replaced by an intermolecular crosslink. 
   
     
     
         2 .- 62 . (canceled)