DOE Patents title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Convergent synthesis of proteins by kinetically controlled ligation

Abstract

The present invention concerns methods and compositions for synthesizing a polypeptide using kinetically controlled reactions involving fragments of the polypeptide for a fully convergent process. In more specific embodiments, a ligation involves reacting a first peptide having a protected cysteyl group at its N-terminal and a phenylthioester at its C-terminal with a second peptide having a cysteine residue at its N-termini and a thioester at its C-termini to form a ligation product. Subsequent reactions may involve deprotecting the cysteyl group of the resulting ligation product and/or converting the thioester into a thiophenylester.

Inventors:
 [1];  [1];  [2];  [1];  [1]
  1. Chicago, IL
  2. Boston, MA
Issue Date:
Research Org.:
The University of Chicago (Chicago, IL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1014499
Patent Number(s):
7674881
Application Number:
U S Patent Application 11/545,923
Assignee:
The University of Chicago (Chicago, IL)
Patent Classifications (CPCs):
C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07K - PEPTIDES
DOE Contract Number:  
FG02-04ER63786
Resource Type:
Patent
Country of Publication:
United States
Language:
English

Citation Formats

Kent, Stephen, Pentelute, Brad, Bang, Duhee, Johnson, Erik, and Durek, Thomas. Convergent synthesis of proteins by kinetically controlled ligation. United States: N. p., 2010. Web.
Kent, Stephen, Pentelute, Brad, Bang, Duhee, Johnson, Erik, & Durek, Thomas. Convergent synthesis of proteins by kinetically controlled ligation. United States.
Kent, Stephen, Pentelute, Brad, Bang, Duhee, Johnson, Erik, and Durek, Thomas. Tue . "Convergent synthesis of proteins by kinetically controlled ligation". United States. https://www.osti.gov/servlets/purl/1014499.
@article{osti_1014499,
title = {Convergent synthesis of proteins by kinetically controlled ligation},
author = {Kent, Stephen and Pentelute, Brad and Bang, Duhee and Johnson, Erik and Durek, Thomas},
abstractNote = {The present invention concerns methods and compositions for synthesizing a polypeptide using kinetically controlled reactions involving fragments of the polypeptide for a fully convergent process. In more specific embodiments, a ligation involves reacting a first peptide having a protected cysteyl group at its N-terminal and a phenylthioester at its C-terminal with a second peptide having a cysteine residue at its N-termini and a thioester at its C-termini to form a ligation product. Subsequent reactions may involve deprotecting the cysteyl group of the resulting ligation product and/or converting the thioester into a thiophenylester.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {2010},
month = {3}
}

Works referenced in this record:

9-(2-Sulfo)fluorenylmethyloxycarbonyl chloride, a new reagent for the purification of synthetic peptides
journal, December 1978


Synthesis of Peptides and Proteins without Cysteine Residues by Native Chemical Ligation Combined with Desulfurization
journal, January 2001


Site-Selective N-Methylation of Peptides on Solid Support
journal, March 1997


Direct On-Resin Synthesis of Peptide- α Thiophenylesters for Use in Native Chemical Ligation
journal, March 2006


Direct Production of Proteins with N-Terminal Cysteine for Site-Specific Conjugation
journal, May 2004


Insights into the Mechanism and Catalysis of the Native Chemical Ligation Reaction
journal, May 2006


S-2-(2,4-dinitrophenyl)ethyl--cysteine: a new derivative for solid-phase peptide synthesis
journal, April 1992


Synthesis of Native Proteins by Chemical Ligation
journal, June 2000


A One-Pot Total Synthesis of Crambin
journal, May 2004


Extending Synthetic Access to Proteins with a Removable Acyl Transfer Auxiliary
journal, May 2002


Chemoselective Amide Ligations by Decarboxylative Condensations ofN-Alkylhydroxylamines and α-Ketoacids
journal, February 2006


Convergent protein synthesis
journal, October 2003


Modulation of Reactivity in Native Chemical Ligation through the Use of Thiol Additives
journal, May 1997


Extending the Applicability of Native Chemical Ligation
journal, January 1996


Primary structure of the hydrophobic plant protein crambin
journal, September 1981


Protein synthesis by native chemical ligation: Expanded scope by using straightforward methodology
journal, August 1999


Total Chemical Synthesis of Crambin
journal, February 2004


Synthesis of Glycoproteins
journal, February 2002


The Cyclization and Polymerization of Bacterially Expressed Proteins Using Modified Self-splicing Inteins
journal, June 1999


Chemical Synthesis of Proteins
journal, June 2005


Accurate protein crystallography at ultra-high resolution: Valence electron distribution in crambin
journal, March 2000


Chemical Protein Synthesis by Solid Phase Ligation of Unprotected Peptide Segments
journal, September 1999


Total Chemical Synthesis, Folding, and Assay of a Small Protein on a Water-Compatible Solid Support
journal, May 2006


In situ neutralization in Boc-chemistry solid phase peptide synthesis: Rapid, high yield assembly of difficult sequences
journal, September 1992


HPLC of Peptides and Proteins: Basic Theory and Methodology
book, January 2004


Total Chemical Synthesis of a Unique Transcription Factor-Related Protein: cMyc-Max
journal, March 1995


Synthesis of a thioester linker precursor for a general preparation of peptide C-terminal thioacids
journal, March 2004


Total synthesis of cytochrome b562 by native chemical ligation using a removable auxiliary
journal, June 2001


2-(4-Nitrophenyl)sulfonylethoxycarbonyl (Nsc) group as a base-labile α-amino protection for solid phase peptide synthesis
journal, October 1994


Toward Fully Synthetic Glycoproteins by Ultimately Convergent Routes:  A Solution to a Long-Standing Problem
journal, June 2004


His6 tag-assisted chemical protein synthesis
journal, March 2005


Synthesis and Application of Unprotected Cyclic Peptides as Building Blocks for Peptide Dendrimers
journal, March 1997


Protein arrays: The current state-of-the-art
journal, January 2003


Synthesis of proteins by native chemical ligation
journal, November 1994


Chemical Ligation of Multiple Peptide Fragments Using a New Protection Strategy
book, January 2001


Design and Chemical Synthesis of a Homogeneous Polymer-Modified Erythropoiesis Protein
journal, February 2003


[13] Protein synthesis by chemical ligation of unprotected peptides in aqueous solution
book, January 1997


Synthetic glycopeptides and glycoproteins as tools for biology
journal, January 2005


A novel amino protection–deprotection procedure and its application in solid phase peptide synthesis
journal, January 1993


Total Chemical Synthesis and X-ray Crystal Structure of a Protein Diastereomer: [D-Gln 35]Ubiquitin
journal, June 2005


Semisynthesis of Proteins by Expressed Protein Ligation
journal, June 2003