Solid phase peptides synthesis processes and associated systems

Patent metadata

Field	Value
Publication number	US-9868759-B2
Application number	US-201514853683-A
Country	US
Kind code	B2
Filing date	Sep 14, 2015
Priority date	Mar 15, 2013
Publication date	Jan 16, 2018
Grant date	Jan 16, 2018

Abstract

Systems and processes for performing solid phase peptide synthesis are generally described. Solid phase peptide synthesis is a known process in which amino acid residues are added to peptides that have been immobilized on a solid support. In certain embodiments, the inventive systems and methods can be used to perform solid phase peptide synthesis quickly while maintaining high yields. Certain embodiments relate to processes and systems that may be used to heat, transport, and/or mix reagents in ways that reduce the amount of time required to perform solid phase peptide synthesis.

First claim

What is claimed is:

1. A process for adding amino acid residues to peptides, comprising:
flowing a first stream comprising amino acids;
flowing a second stream comprising an amino acid activating agent;
merging the first and second streams to form a mixed fluid comprising activated amino acids; and
within about 30 seconds after merging the first and second streams to fotra the mixed fluid, exposing the mixed fluid to a plurality of peptides immobilized on a solid support.

2. The process of claim 1 , wherein the amino acid activating agent comprises an alkaline liquid, a carbodiimide, and/or a uronium activating agent.

3. The process of claim 1 , wherein the solid support comprises polystyrene and/or polyethylene glycol.

4. The process of claim 1 , wherein the solid support comprises a resin.

5. The process of claim 4 , wherein the solid support comprises a microporous polystyrene resin.

6. The process of claim 1 , wherein the solid support is contained within a packed column and/or a fluidized bed.

7. The process of claim 1 , wherein an amino acid residue is added to at least about 99% of the immobilized peptides after exposing the mixed fluid to the immobilized peptides.

8. The process of claim 7 , wherein multiple copies of the amino acid residue are bonded to fewer than about 1% of the immobilized peptides after exposing the mixed fluid to the immobilized peptides.

9. The process of claim 7 , wherein adding the amino acid residue to the immobilized peptides comprises adding a single amino acid residue to the immobilized peptides.

10. The process of claim 7 , wherein adding the amino acid residue to the immobilized peptides comprises adding a peptide comprising two or more amino acid residues to the immobilized peptides.

11. The process of claim 1 , comprising exposing the mixed fluid to the plurality of peptides immobilized on the solid support within about 15 seconds after merging the first and second streams to form the mixed fluid.

12. The process of claim 1 , comprising exposing the mixed fluid to the plurality of peptides immobilized on the solid support within about 10 seconds after merging the first and second streams to form the mixed fluid.

13. The process of claim 1 , comprising exposing the mixed fluid to the plurality of peptides immobilized on the solid support within about 5 seconds after merging the first and second streams to form the mixed fluid.

14. The process of claim 1 , wherein the amino acids comprise protection groups.

15. The process of claim 14 , wherein amine groups of the amino acids are protected.

16. The process of claim 14 , wherein the protection groups comprise fluorenylmethyloxycarbonyl protection groups.

17. The process of claim 14 , wherein the protection groups comprise tertbutyloxycarbonyl protection groups.

18. The process of claim 14 , wherein the protection groups comprise allyloxycarbonyl protection groups.

19. The process of claim 14 , wherein the protection groups comprise carboxybenzyl protection groups.

Assignees

• Massachusetts Inst Technology

Inventors

• Simon Mark David
• Pentelute Bradley L
• Adamo Andrea
• Heider Patrick Louis
• Jensen Klavs F

Classifications

• C07K1/042

  characterised by the nature of the carrier · CPC title

• C07K1/04

  on carriers {(C07K1/003, C07K1/006 take precedence)} · CPC title

• C07K1/045 Primary

  using devices to improve synthesis, e.g. reactors, special vessels · CPC title

• C07K1/08

  using activating agents {(C07K1/003, C07K1/006 take precedence)} · CPC title

• C07K1/061

  using protecting groups · CPC title