System and method for solution phase gap peptide synthesis

Patent metadata

Field	Value
Publication number	US-10947267-B2
Application number	US-201615739391-A
Country	US
Kind code	B2
Filing date	Dec 21, 2016
Priority date	Dec 21, 2015
Publication date	Mar 16, 2021
Grant date	Mar 16, 2021

Abstract

Disclosed is a system and method for Fmoc/tBu solution-phase peptide synthesis including the development of a new benzyl-type GAP protecting group, and related uses thereto. This novel GAP protecting group is utilized in place of a polymer support, facilitating C to N Fmoc peptide synthesis without chromatography, recrystallization, or polymer supports. The GAP group can be added and removed in high yield.

First claim

What is claimed is:

1. A method of attaching a protecting group to an amino acid, wherein the method comprises:
reacting a protecting group selected from the group consisting of:

wherein:

R is selected from the group consisting of: H, Me, and OMe;
Y is selected from the group consisting of S and NH in 1B, or
Y is selected from the group consisting of: O, S, and NH in 1C, 1D and 1E; and
X is selected from the group consisting of: O, S, and NH
with the amino acid to form:

wherein Pg is a protecting group and Z is a general variable.

2. The method of claim 1 , wherein the method comprises the steps of:

wherein BnDppOH is a protecting group selected from 1C, 1D, or 1E; and
wherein Pg is selected from the group consisting of: Cbz, Fmoc, Boc, Bn, Fm, and tBu.

3. The method of claim 1 , wherein the method comprises the steps of:

wherein BnDpp YH is a protecting group selected from 1C, 1D, or 1E; and
wherein Pg is selected from the group consisting of: Cbz, Fmoc, Boc, Bn, Fm, and tBu.

4. The method of claim 1 , wherein the method comprises the steps of:

wherein BnDppYH is a protecting group selected from 1C, 1D, or 1E; and
wherein Pg is selected from the group consisting of: Cbz, Fmoc, Boc, Bn, Fm, and tBu.

5. The method of claim 1 , wherein the method comprises the steps of:

wherein BzDppOH is a protecting group selected from 1C, 1D, or 1E; and
wherein Pg is selected from the group consisting of: Cbz, Fmoc, Boc, Bn, Fm, and tBu.

6. The method of claim 5 , wherein the protecting group is selected from the group consisting of:

wherein R is selected from the group consisting of: H, Me, and OMe; and
wherein X is selected from the group consisting of: O, S, and NH.

7. A method of performing a Group Assisted Purification (GAP) peptide synthesis, wherein the method comprises the steps of attaching a protecting group to an amino acid followed by Fmoc-tBu-based solution phase peptide synthesis (SolPPS) coupling reactions on the resulting amino acid having the attached protecting group, wherein the protecting group is selected from the group consisting of:

wherein:
R is selected from the group consisting of: H, Me, and OMe;
Y is selected from the group consisting of: S and NH for 1B; or
Y is selected from the group consisting of: O, S, and NH for 1C, 1D and 1E, and
X is selected from the group consisting of: O, S, and NH.

8. The method of claim 7 , wherein the Fmoc-tBu-based solution phase peptide synthesis (SolPPS) coupling reaction occurs in ethyl acetate.

9. The method of claim 7 , wherein the Fmoc-tBu-based solution phase peptide synthesis (SolPPS) coupling reaction occurs in dichloromethane.

Assignees

• Univ Texas Tech System

Inventors

• Li Guigen
• Seifert Cole

Classifications

• C07K1/062 Primary

  for alpha- or omega-carboxy functions · CPC title

• C07K1/061 Primary

  using protecting groups · CPC title

• C07F9/5325

  Aromatic phosphine oxides or thioxides (P-C aromatic linkage) · CPC title

• C07F9/36

  Amides thereof · CPC title

• C07F9/3282 Primary

  Esters with hydroxyaryl compounds · CPC title