Stitched polypeptides

1. A method of preparing an alpha-helical polypeptide, said method comprising the steps of:

(i) providing an amino acid of Formula (A):

or a salt thereof;

(ii) providing an amino acid of the Formula (B):

or a salt thereof;

(iii) providing an amino acid of the Formula (C):

or a salt thereof;

(iv) providing at least one additional amino acid;

(v) coupling said amino acids of Formulae (A), (B), and (C) with at least one amino acid of step (iv); and

(vi) treating the polypeptide of step (v) with a catalyst;

wherein

each instance of L 1 and L 2 is, independently, a straight chain alkylene of 1 to 7 carbon atoms;

K is a straight chain alkylene of 1 to 7 carbon atoms;

M is a straight chain alkylene of 1 to 7 carbon atoms;

each instance of R a is, independently, hydrogen; cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic; cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; cyclic or acyclic, substituted or unsubstituted acyl; or an amino protecting group;

R b is hydrogen; cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic;

each instance of R c , is, independently, hydrogen; cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic; cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; cyclic or acyclic, substituted or unsubstituted acyl; substituted or unsubstituted hydroxyl; substituted or unsubstituted thiol; substituted or unsubstituted amino; cyano; isocyano; halo; or nitro;

each instance of R e is, independently, —R E , wherein each instance of —R E is, independently, hydrogen, cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic; cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; substituted or unsubstituted acyl; a resin; or a hydroxyl protecting group;

each instance of R f is, independently, hydrogen; cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic; cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; substituted or unsubstituted acyl; a resin; an amino protecting group; or a label optionally joined by a linker, wherein the linker is selected from cyclic or acyclic, branched or unbranched, substituted or unsubstituted alkylene; cyclic or acyclic, branched or unbranched, substituted or unsubstituted alkenylene; cyclic or acyclic, branched or unbranched, substituted or unsubstituted alkynylene; cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroalkylene; cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroalkenylene; cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroalkynylene; substituted or unsubstituted arylene; substituted or unsubstituted heteroarylene; or substituted or unsubstituted acylene;

or R f and R a together form a substituted or unsubstituted heterocyclic or heteroaromatic ring; and

each instance of x is, independently, an integer between 0 to 3, inclusive.

2. The method of claim 1 , wherein said catalyst is a ring closing metathesis catalyst.

3. The method of claim 1 , wherein said catalyst is a ruthenium catalyst.

4. The method of claim 1 , wherein each R a is hydrogen or methyl.

5. The method of claim 1 , wherein each R a is hydrogen.

6. The method of claim 1 , wherein at least one R a is —COCH 3 .

7. The method of claim 1 , wherein each W is alkyl.

8. The method of claim 1 , wherein each R b is methyl.

9. The method of claim 1 , wherein each R f is hydrogen.

10. The method of claim 1 , wherein each R e is hydrogen.

11. The method of claim 1 , wherein each R f is an amino protecting group.

12. The method of claim 1 , wherein each R f is Boc.

13. The method of claim 1 , wherein each R f is Fmoc.

14. The method of claim 1 , wherein each is a double bond.

15. The method of claim 1 , wherein the amino acid of Formula (A) is an amino acid of Formula (A-2):

16. The method of claim 15 , wherein the amino acid of Formula (A-2) is of one of the following formulae:

17. The method of claim 1 , wherein an amino acids of Formulae (B) and (C) are independently of one of the following formulae:

18. The method of claim 1 , wherein an amino acids of Formulae (B) and (C) are independently of one of the following formulae: