System and method for solution phase gap peptide synthesis
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.
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.