Preparation of functional homocysteine residues in polypeptides and peptides
View Patent ↗Methodology was developed for transformation of methionine residues into homocysteine derivatives. Methionine residues can undergo alkylation reactions at low pH to yield sulfonium ions, which can then be selectively demethylated to give alkyl homocysteine residues. This process tolerates many functional groups.
1. A polypeptide comprising one or more R—C H residues, wherein each R—C H residue in the polypeptide has the following structure:
wherein:
R X , independently for each R—C H residue, is H or alkyl; and
R, independently for each R—C H residue is:
i) a moiety with the following structure:
wherein R′ is selected from alkoxy,
or
ii) a moiety with the following structure:
wherein R′ is selected from alkoxy,
2. The polypeptide of claim 1 , wherein the polypeptide is a homopolymer.
3. The polypeptide of claim 1 , wherein the polypeptide is a heteropolymer.
4. The polypeptide of claim 1 , wherein the polypeptide does not comprise a residue that is not an R—C H residue.
5. The polypeptide of claim 1 , wherein the polypeptide comprises at least 4 residues or at least 10 residues.
6. The polypeptide of claim 1 , wherein the polypeptide comprises at least 60 residues.
7. A polypeptide having the following structure:
8. The polypeptide of claim 1 , wherein R is a moiety with the following structure:
wherein R′ is selected from alkoxy,
9. The polypeptide of claim 1 , wherein R is a moiety with the following structure:
wherein R′ is selected from alkoxy,
10. A polypeptide comprising one or more R—C H residues, wherein each R—C H residue in the polypeptide has the following structure:
wherein:
R X , independently for each R—C H residue, is H or alkyl:
R 1 , independently for each R—C H residue, is selected from H, alkyl, acyl, and alkoxy-C(O)—;
R 2 , independently for each R—C H residue, is selected from H, alkyl, acyl, and alkoxy-C(O)—; and
n, independently for each R—C H residue, is an integer from 0-10.
11. The polypeptide of claim 10 , wherein R X is H, R 1 is H; R 2 is H, C 1-3 alkyl, or Ac; and n is 1, 2, or 3.
12. A polypeptide comprising one or more R—C H residues, wherein each R—C H residue in the polypeptide has the following structure:
wherein:
R X , independently for each R—C H residue, is H or alkyl:
R, independently for each R—C H residue, is alkyl:
provided that at least one R—C H residue is
and wherein x + is a counterion.
13. The polypeptide of claim 1 , wherein the polypeptide is
and wherein X + is a counterion.
14. The polypeptide of claim 1 , further comprising at least one M residue and at least one M R residue, wherein the M and M R residues are no more than 10% of the M, M R , and R—C H residues in the polypeptide.