Modification of peptides via S

1. A compound

(a) comprising substructure I:

wherein, independently for each occurrence,

A 1 is H, an amine protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

A 2 , A 3 , and A 4 are selected from the group consisting of a natural amino acid, an unnatural amino acid, and a plurality of natural amino acids or unnatural amino acids;

x is 0, 1, 2, 3, 4, 5, or 6;

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein; and

is a perfluorinated aryl para-substituted diradical; and

R is H or alkyl;

(b) comprising substructure II:

wherein, independently for each occurrence,

A 1 is H, an amine protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

A 2 , A 3 , and A 4 are selected from the group consisting of a natural amino acid, an unnatural amino acid, and a plurality of natural amino acids or unnatural amino acids;

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

is a perfluorinated aryl para-substituted diradical;

x is 0, 1, 2, 3, 4, 5, or 6;

m is 1, 2, 3, 4, 5, or 6; and

R is H or alkyl;

(c) comprising substructure III:

wherein, independently for each occurrence,

A 1 is H, an amine protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

is a perfluorinated aryl para-substituted diradical;

x is 0, 1, 2, 3, 4, 5, or 6;

R is H or alkyl; and

R 1 is H, alkyl, alkylthioalkyl, aralkyl, heteroaralkyl, hydroxyaralkyl, HO 2 C-alkyl, H 2 N—C(O)-alkyl, heterocycloalkyl, guanidinylalkyl, aminoalkyl, or hydroxyalkyl;

(d) comprising substructure IV:

wherein, independently for each occurrence,

A 1 is H, an amine protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

x is 0, 1, 2, 3, 4, 5, or 6;

is a perfluorinated aryl para-substituted diradical; and

R is H or alkyl;

(e) comprising substructure V:

wherein, independently for each occurrence,

A 1 is H, an amine protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

A 2 , A 3 , and A 4 are selected from the group consisting of a natural amino acid, an unnatural amino acid, and a plurality of natural amino acids or unnatural amino acids;

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

x is 0, 1, 2, 3, 4, 5, or 6;

is a perfluorinated aryl para-substituted diradical; and

R is H or alkyl; or

(f) comprising substructure VI:

wherein, independently for each occurrence,

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

is a perfluorinated aryl para-substituted diradical;

x is 0, 1, 2, 3, 4, 5, or 6;

R is H or alkyl; and

R 1 is H, alkyl, alkylthioalkyl, aralkyl, heteroaralkyl, hydroxyaralkyl, HO 2 C-alkyl, H 2 N—C(O)-alkyl, heterocycloalkyl, guanidinylalkyl, aminoalkyl, or hydroxyalkyl.

2. The compound of claim 1 , wherein none of A 1 , A 2 , A 3 , A 4 , and A 5 comprises cysteine.

3. The compound of claim 1 , wherein one or more of A 1 , A 2 , A 3 , A 4 , and A 5 comprises arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, or tryptophan.

4. The compound of claim 1 , wherein

is 2,3,5,6-tetrafluorophenylene or 2,2′,3,3′,5,5′,6,6′-octafluoro-1,1′-biphenyl-4,4′-ene.

5. The compound of claim 1 , wherein R is H.

6. The compound of claim 1 , wherein m is 2, 3, or 4.

7. The compound of claim 1 , wherein R 1 is aminoalkyl or aralkyl.

8. The compound of claim 1 , wherein the compound comprising substructure I is selected from the group consisting of (SEQ ID NOS 7-18, respectively, in order of appearance):

9. The compound of claim 1 , wherein the compound comprising substructure I is selected from the group consisting of (SEQ ID NOS 19-21, respectively, in order of appearance):

wherein X is H or β-Ala-FITC.

10. The compound of claim 1 , wherein the compound comprising substructure II is selected from the group consisting of (SEQ ID NOS 22-23, respectively, in order of appearance):

11. The compound of claim 1 , wherein the compound comprising substructure VI is (SEQ ID NOS 24-25, respectively, in order of appearance)

12. A compound comprising substructure XI or XII:

wherein, independently for each occurrence,

A 1 is H, an amine protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

A 2 is selected from the group consisting of a natural amino acid, an unnatural amino acid, and a plurality of natural amino acids or unnatural amino acids;

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

is a perfluorinated aryl para-substituted diradical;

x is 0, 1, 2, 3, 4, 5, or 6;

R is H or alkyl; and

L is a substituted or unsubstituted alkyl diradical, a substituted or unsubstituted aryl diradical, or a substituted or unsubstituted aralkyl diradical.

13. The compound of claim 12 , wherein the compound of substructure XI is (SEQ ID NO: 30):

14. A method of making a compound

(a) according to Scheme 1, wherein the compound comprises substructure I:

wherein, independently for each occurrence,

A 1 is H, an amine protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

A 2 , A 3 , and A 4 are selected from the group consisting of a natural amino acid, an unnatural amino acid, and a plurality of natural amino acids or unnatural amino acids;

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

R is H or alkyl;

x is 0, 1, 2, 3, 4, 5, or 6;

is a perfluorinated aryl compound; and

is a perfluorinated aryl para-substituted diradical;

(b) according to Scheme 2, wherein the compound comprises substructure II:

wherein, independently for each occurrence,

A 1 is H, an amine protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

A 2 , A 3 , and A 4 are selected from the group consisting of a natural amino acid, an unnatural amino acid, and a plurality of natural amino acids or unnatural amino acids;

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

R is H or alkyl;

x is 0, 1, 2, 3, 4, 5, or 6;

is a perfluorinated aryl radical;

m is 1, 2, 3, 4, 5, or 6; and

is a perfluorinated aryl para-substituted diradical;

(c) according to Scheme 3, wherein the compound comprises substructure III:

wherein, independently for each occurrence,

A 1 is H, an amine protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

R is H or alkyl;

x is 0, 1, 2, 3, 4, 5, or 6;

is a perfluorinated aryl radical;

R 1 is H, alkyl, alkylthioalkyl, aralkyl, heteroaralkyl, hydroxyaralkyl, HO 2 C-alkyl, H 2 N—C(O)-alkyl, heterocycloalkyl, guanidinylalkyl, aminoalkyl, or hydroxyalkyl; and

is a perfluorinated aryl para-substituted diradical;

(d) according to Scheme 4, wherein the compound comprises substructure IV:

wherein, independently for each occurrence,

A 1 is H, an amine protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

R is H or alkyl;

x is 0, 1, 2, 3, 4, 5, or 6;

is a perfluorinated aryl radical; and

is a perfluorinated aryl para-substituted diradical;

(e) according to Scheme 5, wherein the compound comprises substructure V:

wherein, independently for each occurrence,

A 1 is H, an amine protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

A 2 , A 3 , and A 4 are selected from the group consisting of a natural amino acid, an unnatural amino acid, and a plurality of natural amino acids or unnatural amino acids;

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

R is H or alkyl;

x is 0, 1, 2, 3, 4, 5, or 6;

is a perfluorinated aryl radical; and

is a perfluorinated aryl para-substituted diradical; or

(f) according to Scheme 6, wherein the compound comprises substructure VI:

wherein, independently for each occurrence,

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

R is H or alkyl;

x is 0, 1, 2, 3, 4, 5, or 6;

R 1 is H, alkyl, alkylthioalkyl, aralkyl, heteroaralkyl, hydroxyaralkyl, HO 2 C-alkyl, H 2 N—C(O)-alkyl, heterocycloalkyl, guanidinylalkyl, aminoalkyl, or hydroxyalkyl;

is a perfluorinated aryl radical; and

is a perfluorinated aryl para-substituted diradical.

15. The method of claim 14 , wherein A 5 does not comprise cysteine.

16. The method of claim 14 , wherein none of A 1 , A 2 , A 3 , A 4 , and A 5 comprises cysteine.

17. The method of claim 14 , wherein one or more of A 1 , A 2 , A 3 , A 4 , and A 5 comprises arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, or tryptophan.

18. The method of claim 14 , wherein

is hexafluorophenyl or decafluorobiphenyl.

19. The method of claim 14 , wherein

is 2,3,5,6-tetrafluorophenylene or 2,2′,3,3′,5,5′,6,6′-octafluoro-1,1′-biphenyl-4,4′-ene.

20. The method of claim 14 , wherein R is H.

21. The method of claim 14 , wherein m is 2, 3, or 4.

22. The method of claim 14 , wherein R 1 is aminoalkyl or aralkyl.

23. The method of claim 14 , wherein

is pentafluorophenyl or 4′-(2,2′,3,3′,4,5,5′,6,6′-nonafluoro-1,1′-biphenyl).

24. A method of making a compound according to Scheme 7:

wherein, independently for each occurrence,

A 1 is H, an amine protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

A 5 is OH, a carboxylate protecting group, a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

R is H or alkyl;

x is 0, 1, 2, 3, 4, 5, or 6;

is a perfluorinated aryl radical; and

is a perfluorinated aryl para-substituted diradical.

25. A method of disrupting or inhibiting the p53/MDM2 interaction or enhancing the activity of p53 in a cell comprising the step of:

contacting the cell with an effective amount of a compound of claim 1 , thereby disrupting or inhibiting the p53/MDM2 interaction or enhancing the activity of p53.

26. A method of treating cancer in a subject in need thereof comprising the step of:

administering to the subject a compound of claim 1 in an amount effective to (i) disrupt or inhibit the interaction of p53 and MDM2 in a cancer cell, or (ii) enhance the activity of p53 in a cancer cell,

thereby treating the cancer.

27. A method of disrupting or inhibiting the p53/MDM2 interaction or enhancing the activity of p53 in a cell comprising the step of:

contacting the cell with an effective amount of a compound of claim 12 , thereby disrupting or inhibiting the p53/MDM2 interaction or enhancing the activity of p53.

28. A method of treating cancer in a subject in need thereof comprising the step of:

administering to the subject a compound of claim 12 in an amount effective to (i) disrupt or inhibit the interaction of p53 and MDM2 in a cancer cell, or (ii) enhance the activity of p53 in a cancer cell,

thereby treating the cancer disease.

29. The method of claim 26 , wherein the cancer is a glioma.

30. The method of claim 26 , wherein the cancer is glioblastoma.

31. The method of claim 28 , wherein the cancer is a glioma.

32. The method of claim 28 , wherein the cancer is glioblastoma.