Process for preparation of a peptide

Patent metadata

Field	Value
Publication number	US-11053277-B2
Application number	US-201716474678-A
Country	US
Kind code	B2
Filing date	Dec 28, 2017
Priority date	Dec 28, 2016
Publication date	Jul 6, 2021
Grant date	Jul 6, 2021

Abstract

The present invention relates to a novel process for preparation of peptides having amino acid chain length in the range of 2-40 comprises the steps: i) attaching an end-blocked amino acid with an ionic liquid based solid support in presence of an ionic solvent to obtain an end-terminal blocked amino acid attached ionic liquid; ii) removing end-terminal blocking agent from the end-terminal blocked amino acid attached ionic liquid of step i) followed by work up to obtain an amino acid attached ionic liquid; iii) repeating steps i) through ii) one or more times to obtain a polypeptide attached ionic liquid; and iv) detaching the polypeptide from the polypeptide attached ionic liquid of step iii) to obtain the polypeptide. Said process does not use any auxiliary reagents like dehydrating agent or activating agent. The use of ionic liquids as supports as well as solvents result in the faster kinetics of the process, the separation issues are reduced, and the process has no racemization issues.

First claim

We claim:

1. A process for preparation of a peptide having an amino acid chain length of from 2-40 amino acids, said process comprising:
i) attaching a first terminal-blocked amino acid to an ionic liquid based solid support in the presence of an ionic solvent to obtain a terminal blocked amino acid attached ionic liquid;
ii) removing a terminal blocking group from the terminal blocked amino acid attached ionic liquid to obtain an amino acid attached ionic liquid;
iii) attaching a second terminal blocked amino acid to the amino acid attached ionic liquid and thereafter removing the terminal blocking group, repeatedly, to obtain an ionic liquid attached with a peptide having an amino acid chain length of from 2 to 40 amino acids; and
iv) detaching said peptide from the ionic liquid based solid support, wherein the C-terminal blocked amino acid and wherein the N-terminal blocked amino acid have multiple functionality selected from cationic functionality and ionic liquid functionality
wherein the ionic liquid based solid support comprises a) a heteroatom containing a cationic functionality selected from the group consisting of diethanolamine, triethylamine, triethanolamine, diethyl amine and triethylphosphine and combinations thereof; b) a side chain containing from 2-8 —CH 2 groups and combinations thereof; c) a side chain end group functionality selected from the group consisting of —Cl, —Br, —OH, —I and combinations thereof;
wherein the preparation of a peptide is N-terminal or C-terminal peptide synthesis approach; wherein the process is free of dehydrating, activating agents and peptide hydrolase.

2. The process as claimed in claim 1 , comprising attaching the first terminal-blocked amino acid to the ionic liquid based solid support by contacting the ionic liquid based solid support with the terminal blocked amino acid for a time period of from 2 to 4 hours.

3. The process as claimed in claim 1 , comprising attaching the first terminal-blocked amino acid with the ionic liquid based solid support at a temperature of from 27° C. to 60° C.

4. The process as claimed in claim 1 , wherein said ionic solvent is triethylamine, diethanolamine, triethanolamine, diethyl amine, imidazole, or a triethylphosphine based functionalized ionic liquid.

5. The process as claimed in claim 1 , wherein the terminal blocking group is selected from the group consisting of an ester, an ether, a carbamate, and an acid chloride linkage.

6. The process as claimed in claim 1 , wherein the process has a water content is from 1 to 40%.

7. The process as claimed in claim 1 , wherein the preparation is N-terminal approach, comprising detaching the peptide from the ionic liquid by reacting said peptide with a base selected from the group consisting of sodium hydroxide, potassium hydroxide, and lithium hydroxide and combinations thereof for from 30 mins to 2 hours in a solvent selected from the group consisting of tetrahydrofuran, water, and ethanol and combinations thereof.

8. The process as claimed in claim 1 , wherein the preparation is C-terminal approach, comprising detaching the peptide from the ionic liquid by reacting said peptide with an acid selected from the group consisting of trifluoroacetic acid, acetic acid, and trifluromethane sulfonic acid and combinations thereof for from 30 mins to 2 hour in a solvent selected from the group consisting of tetrahydrofuran, water, and ethanol and combinations thereof.

9. The process of claim 1 , wherein said side chain contains from 2 to 6 —CH 2 groups.

10. The process of claim 9 , wherein said side chain contains from 2-4 —CH 2 groups.

11. The process of claim 6 , wherein the water content is from 1-20%.

12. The process of claim 11 , wherein the water content is from 1 to 5%.

Assignees

• Indian Institute Tech Delhi

Inventors

• Upadhyayula Sreedevi
• Patra Tanmoy
• Paul Subhasis

Classifications

• C07K5/06078

  and aromatic or cycloaliphatic · CPC title

• C07K7/06

  having 5 to 11 amino acids · CPC title

• C07K1/042 Primary

  characterised by the nature of the carrier · CPC title

• C07K7/08

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title