Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

Synthesis of peptide .alpha.-thioesters

Patent ·
OSTI ID:943347

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.

Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA
Sponsoring Organization:
United States Department of Energy
DOE Contract Number:
W-7405-ENG-48
Assignee:
Lawrence Livermore National Security, LLC (Livermore, CA)
Patent Number(s):
7,414,106
Application Number:
10/871,346
OSTI ID:
943347
Country of Publication:
United States
Language:
English

References (3)

Peptide Syntheses Via Amino Acid Active Esters 1 journal August 1959
Solid-Phase Synthesis of Lipidated Peptides journal May 2002
Biosynthesis of a Head-to-Tail Cyclized Protein with Improved Biological Activity journal June 1999

Similar Records

A Fmoc-compatible Method for the Solid-Phase Synthesis of Peptide C-Terminal (alpha)-Thioesters based on the Safety-Catch Hydrazine Linker
Journal Article · Fri Nov 21 23:00:00 EST 2003 · Journal of Organic Chemistry · OSTI ID:15014401

Non-technical write-up of summer research for the Department of Homeland Security
Technical Report · Fri Jul 29 00:00:00 EDT 2005 · OSTI ID:881664

Preparation of Peptide p-Nitroanilides using an Aryl Hydrazine Solid Support
Journal Article · Thu Aug 05 00:00:00 EDT 2004 · Organic Letters · OSTI ID:15014528