Method for atomic layer deposition

Patent metadata

Field	Value
Publication number	US-9605344-B2
Application number	US-201414917566-A
Country	US
Kind code	B2
Filing date	Sep 12, 2014
Priority date	Sep 15, 2013
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

Abstract

An atomic layer deposition method is disclosed for preparing polypeptides. The method comprises providing a solid-phase support comprising a reactive amine monolayer in an atomic layer deposition (ALD) chamber. The solid-phase support is contacted with a first protected amino acid substituted with a protecting group by atomic layer deposition, wherein the protecting group is bonded to a non-side chain amino group of the protected amino acid. A carboxylic acid group of the first protected amino acid is reacted with the reactive amine monolayer, thereby coupling the first protected amino acid to the solid-phase support to produce a coupled-product.

First claim

What is claimed is:

1. An atomic layer deposition method for preparing polypeptides, the method comprising:
providing a solid-phase support comprising a reactive amine monolayer in an atomic layer deposition (ALD) chamber;
contacting the solid-phase support with a first protected amino acid substituted with a protecting group by atomic layer deposition, wherein the protecting group is bonded to a non-side chain amino group of the protected amino acid; and
reacting a carboxylic acid group of the first protected amino acid with the reactive amine monolayer, thereby coupling the first protected amino acid to the solid-phase support to produce a coupled-product.

2. The method of claim 1 , wherein the ALD chamber is maintained at a temperature of about 100° C. to about 200° C.

3. The method of claim 2 , wherein the ALD chamber is maintained at a temperature ranging from room temperature to 250° C.

4. The method of claim 2 , wherein the first amino acid is at a temperature ranging from room temperature to 250° C. upon introduction into the ALD chamber.

5. The method of claim 2 , wherein the contacting and reacting steps are carried out at a temperature that is not sufficient to cause decomposition of the first amino acid.

6. The method of claim 1 , wherein the protecting group is a tert-butoxycarbonyl (Boc) group, a carbobenzyloxy (Cbz) group, a benzoyl group (Bz), a fluorenylmethyloxycarbonyl (FMoc) group, a p-Methoxybenzyl carbonyl (Moz or MeOZ) group, a Benzyl (Bn) group, a Carbamate group, a p-Methoxybenzyl (PMB) group, a 3,4-Dimethoxybenzyl (DMPM) group, a p-methoxyphenyl (PMP) group and a Tosyl (Ts) group.

7. The method of claim 1 , wherein the protecting group is a tert-butoxycarbonyl (Boc) group.

8. The method of claim 1 , wherein the protecting group is removed in the presence of an acid.

9. The method of claim 8 , wherein the protecting group is a tert-butoxycarbonyl (Boc) group.

10. The method of claim 1 , wherein the carboxylic acid group of the first protected amino acid is reacted with the reactive amine monolayer in the presence of a coupling agent in an atomic layer deposition (ALD) chamber.

11. The method of claim 10 , wherein the coupling agent comprises at least one compound selected from the group consisting of dicyclohexylcarbodiimide (DCC), 1-hydroxy-benzotriazole (HOBt), 1-hydroxy-7-aza-benzotriazole (HOAt) and diisopropyl-carbodiimide (DIC).

12. The method of claim 10 , wherein the coupling agent is at a temperature ranging from room temperature to about 250° C. upon introduction into the ALD chamber.

13. The method of claim 1 , further comprising:
(a) removing the protecting group, thereby producing a deprotected-coupled-product having a deprotected amino group,
(b) contacting the deprotected-coupled-product with at least a second protected amino acid by atomic layer deposition, wherein the second protected amino acid's non-side chain amino group is protected by a protecting group; and reacting the carboxylic acid group of the second protected amino acid with the deprotected amino group, thereby coupling the second amino acid to the deprotected-coupled product in a monolayer, and
(c) optionally, repeating steps (a) and (b), wherein the second protected amino acid is identical to or different from that of the preceding step (b).

14. The atomic layer deposition method of claim 13 , wherein the protecting group is removed in the presence of a deprotecting agent.

15. The atomic layer deposition method of claim 14 , wherein the deprotecting agent an acid.

16. The atomic layer deposition of claim 14 , wherein the method is carried out in an atomic layer deposition (ALD) chamber and the deprotecting agent is at a temperature of about 70° C. upon introduction into the ALD chamber.

17. The atomic layer deposition method of claim 13 , further comprising:
cleaving polypeptides from the solid-phase support,
optionally, removing all remaining protecting groups on the polypeptides after the cleaving step, and
isolating and optionally, purifying the polypeptides.

18. The atomic layer deposition method of claim 13 , wherein one or more of the first amino acid and the second amino acid do not have a side chain functionality requiring protection.

19. The atomic layer deposition method of claim 1 , wherein the solid-phase support comprises at least one material selected from the group consisting of a silica film, a plurality of silica nanoparticles, porous inorganic materials, porous polymeric materials, or non-porous inorganic materials, non-porous polymeric materials, metallic nanoparticles or quantum dots.

20. The atomic layer deposition method of claim 1 , wherein the solid-phase support comprises a mesoporous silica film.

Assignees

• Stc Unm

Inventors

• Jiang Ying-Bing
• Cecchi Joseph L
• Fu Yaqin
• Brinker C Jeffrey

Classifications

• C23C16/45534 Primary

  Use of auxiliary reactants other than used for contributing to the composition of the main film, e.g. catalysts, activators or scavengers · CPC title

• C23C16/46

  characterised by the method used for heating the substrate (C23C16/48, C23C16/50 take precedence) · CPC title

• C23C16/45525 Primary

  Atomic layer deposition [ALD] · CPC title