Selective Arylation of Dichalcogenides in Biomolecules

Patent metadata

Field	Value
Publication number	US-2016367693-A1
Application number	US-201615187169-A
Country	US
Kind code	A1
Filing date	Jun 20, 2016
Priority date	Jun 19, 2015
Publication date	Dec 22, 2016
Grant date	—

Abstract

Disclosed are chemical transformations for the conjugation of unprotected peptide biomolecules. The processes feature several significant advantages over existing methods of peptide modification, including specificity towards selenocysteine over other nucleophiles (e.g., amines, hydroxyls), excellent functional group tolerance, and mild reaction conditions.

First claim

We claim:

1 . A compound comprising
(a) 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 5 is OH, —O(carboxylate protecting group), a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

is a substituted or unsubstituted aryl or heteroaryl radical;
x is 0, 1, 2, 3, 4, 5, or 6; and
R is H or alkyl; or

(b) 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 5 is OH, —O(carboxylate protecting group), a natural or unnatural amino acid, a peptide, an oligopeptide, a polypeptide, or a protein;

is a substituted or unsubstituted aryl or heteroaryl radical, provided

is not a
perfluoroaryl radical;
x is 0, 1, 2, 3, 4, 5, or 6; and

R is H or alkyl.

2 . The compound of claim 1 , wherein

is a substituted aryl radical.

3 . The compound of claim 1 , wherein

is a substituted phenyl radical.

4 . The compound of claim 1 , wherein

is an unsubstituted aryl radical.

5 . The compound of claim 1 , wherein

is a substituted heteroaryl radical.

6 . The compound of claim 1 , wherein

is a substituted indole, pyrazolo, thiophene, pyrimidine, benzofuran, or isoxazole radical.

7 . The compound of claim 1 , wherein

is an unsubstituted heteroaryl radical.

8 . The compound of claim 1 , wherein

is an unsubstituted indole, pyrazolo, thiophene, pyrimidine, benzofuran, or isoxazole radical.

9 . The compound of claim 1 , wherein

or a regioisomer or stereoisomer thereof.

10 . A compound comprising
(a) 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 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, —O(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 substituted or unsubstituted aryl or heteroaryl diradical; and
R is H or alkyl;

(b) 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 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, —O(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 substituted or unsubstituted aryl or heteroaryl diradical, provided

is not a perfluoroaryl diradical; and
R is H or alkyl;

(c) substructure V or substructure VII:

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, —O(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 substituted or unsubstituted aryl or heteroaryl diradical; and
R is H or alkyl; or

(d) substructure VI or substructure VIII:

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, —O(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 substituted or unsubstituted aryl or heteroaryl diradical, provided

is not a perfluoroaryl diradical; and
R is H or alkyl.

11 . The compound of claim 10 , wherein

is a substituted aryl diradical.

12 . The compound of claim 10 , wherein

Assignees

• Massachusetts Inst Technology

Inventors

• Buchwald Stephen L
• Pentelute Bradley L
• Cohen Daniel T
• Zhang Chi

Classifications

• C07K1/1077 Primary

  by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids · CPC title

• A61K47/6851 Primary

  the antibody targeting a determinant of a tumour cell · CPC title

• C07K1/13

  Labelling of peptides · CPC title

• C07K14/47

  from mammals · CPC title

• C07K1/1075

  by covalent attachment of amino acids or peptide residues · CPC title