Synthesis of peptide .alpha.-thioesters
Abstract
Disclosed herein is a new method for the solid phase peptide synthesis (SPPS) of C-terminal peptide .alpha. thioesters using Fmoc/t-Bu chemistry. This method is based on the use of an aryl hydrazine linker, which is totally stable to conditions required for Fmoc-SPPS. When the peptide synthesis has been completed, activation of the linker is achieved by mild oxidation. The oxidation step converts the acyl-hydrazine group into a highly reactive acyl-diazene intermediate which reacts with an .alpha.-amino acid alkylthioester (H-AA-SR) to yield the corresponding peptide .alpha.-thioester in good yield. A variety of peptide thioesters, cyclic peptides and a fully functional Src homology 3 (SH3) protein domain have been successfully prepared.
- Inventors:
-
- Livermore, CA
- Clayton, CA
- Issue Date:
- Research Org.:
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 943347
- Patent Number(s):
- 7414106
- Application Number:
- 10/871,346
- Assignee:
- Lawrence Livermore National Security, LLC (Livermore, CA)
- Patent Classifications (CPCs):
-
C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07K - PEPTIDES
- DOE Contract Number:
- W-7405-ENG-48
- Resource Type:
- Patent
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
Camarero, Julio A, Mitchell, Alexander R, and De Yoreo, James J. Synthesis of peptide .alpha.-thioesters. United States: N. p., 2008.
Web.
Camarero, Julio A, Mitchell, Alexander R, & De Yoreo, James J. Synthesis of peptide .alpha.-thioesters. United States.
Camarero, Julio A, Mitchell, Alexander R, and De Yoreo, James J. Tue .
"Synthesis of peptide .alpha.-thioesters". United States. https://www.osti.gov/servlets/purl/943347.
@article{osti_943347,
title = {Synthesis of peptide .alpha.-thioesters},
author = {Camarero, Julio A and Mitchell, Alexander R and De Yoreo, James J},
abstractNote = {Disclosed herein is a new method for the solid phase peptide synthesis (SPPS) of C-terminal peptide .alpha. thioesters using Fmoc/t-Bu chemistry. This method is based on the use of an aryl hydrazine linker, which is totally stable to conditions required for Fmoc-SPPS. When the peptide synthesis has been completed, activation of the linker is achieved by mild oxidation. The oxidation step converts the acyl-hydrazine group into a highly reactive acyl-diazene intermediate which reacts with an .alpha.-amino acid alkylthioester (H-AA-SR) to yield the corresponding peptide .alpha.-thioester in good yield. A variety of peptide thioesters, cyclic peptides and a fully functional Src homology 3 (SH3) protein domain have been successfully prepared.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {2008},
month = {8}
}
Works referenced in this record:
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journal, May 2002
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- Journal of the American Chemical Society, Vol. 124, Issue 21
Peptide Syntheses Via Amino Acid Active Esters 1
journal, August 1959
- Goodman, Murray; Stueben, Kenneth C.
- Journal of the American Chemical Society, Vol. 81, Issue 15
Biosynthesis of a Head-to-Tail Cyclized Protein with Improved Biological Activity
journal, June 1999
- Camarero, Julio A.; Muir, Tom W.
- Journal of the American Chemical Society, Vol. 121, Issue 23