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:
-
- Chicago, IL
- 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:
Selective Desulfurization of Cysteine in the Presence of Cys(Acm) in Polypeptides Obtained by Native Chemical Ligation
journal, February 2007
- Pentelute, Brad L.; Kent, Stephen B. H.
- Organic Letters, Vol. 9, Issue 4
9-(2-Sulfo)fluorenylmethyloxycarbonyl chloride, a new reagent for the purification of synthetic peptides
journal, December 1978
- Merrifield, R. B.; Bach, Anita E.
- The Journal of Organic Chemistry, Vol. 43, Issue 25
Synthesis of Peptides and Proteins without Cysteine Residues by Native Chemical Ligation Combined with Desulfurization
journal, January 2001
- Yan, Liang Z.; Dawson, Philip E.
- Journal of the American Chemical Society, Vol. 123, Issue 4
Site-Selective N-Methylation of Peptides on Solid Support
journal, March 1997
- Miller, Stephen C.; Scanlan, Thomas S.
- Journal of the American Chemical Society, Vol. 119, Issue 9
Direct On-Resin Synthesis of Peptide- α Thiophenylesters for Use in Native Chemical Ligation
journal, March 2006
- Bang, Duhee; Pentelute, Brad L.; Gates, Zachary P.
- Organic Letters, Vol. 8, Issue 6
Direct Production of Proteins with N-Terminal Cysteine for Site-Specific Conjugation
journal, May 2004
- Gentle, Ian E.; De Souza, David P.; Baca, Manuel
- Bioconjugate Chemistry, Vol. 15, Issue 3
Insights into the Mechanism and Catalysis of the Native Chemical Ligation Reaction
journal, May 2006
- Johnson, Erik C. B.; Kent, Stephen B. H.
- Journal of the American Chemical Society, Vol. 128, Issue 20
S-2-(2,4-dinitrophenyl)ethyl--cysteine: a new derivative for solid-phase peptide synthesis
journal, April 1992
- Royo, Miriam; García-Echeverría, Carlos; Giralt, Ernest
- Tetrahedron Letters, Vol. 33, Issue 17
Synthesis of Native Proteins by Chemical Ligation
journal, June 2000
- Dawson, Philip E.; Kent, Stephen B. H.
- Annual Review of Biochemistry, Vol. 69, Issue 1
A One-Pot Total Synthesis of Crambin
journal, May 2004
- Bang, Duhee; Kent, Stephen B. H.
- Angewandte Chemie International Edition, Vol. 43, Issue 19
Extending Synthetic Access to Proteins with a Removable Acyl Transfer Auxiliary
journal, May 2002
- Offer, John; Boddy, C. N. C.; Dawson, Philip E.
- Journal of the American Chemical Society, Vol. 124, Issue 17
Chemoselective Amide Ligations by Decarboxylative Condensations ofN-Alkylhydroxylamines and α-Ketoacids
journal, February 2006
- Bode, Jeffrey W.; Fox, Ryan M.; Baucom, Kyle D.
- Angewandte Chemie International Edition, Vol. 45, Issue 8
Convergent protein synthesis
journal, October 2003
- Casi, G.
- Current Opinion in Structural Biology, Vol. 13, Issue 5
Modulation of Reactivity in Native Chemical Ligation through the Use of Thiol Additives
journal, May 1997
- Dawson, Philip E.; Churchill, Michael J.; Ghadiri, M. Reza
- Journal of the American Chemical Society, Vol. 119, Issue 19
Extending the Applicability of Native Chemical Ligation
journal, January 1996
- Canne, Lynne E.; Bark, Steven J.; Kent, Stephen B. H.
- Journal of the American Chemical Society, Vol. 118, Issue 25
Constructing proteins by dovetailing unprotected synthetic peptides: backbone-engineered HIV protease
journal, April 1992
- Schnolzer, M.; Kent, S.
- Science, Vol. 256, Issue 5054
Primary structure of the hydrophobic plant protein crambin
journal, September 1981
- Teeter, Martha M.; Mazer, Jonathan A.; L'Italien, James J.
- Biochemistry, Vol. 20, Issue 19
Protein synthesis by native chemical ligation: Expanded scope by using straightforward methodology
journal, August 1999
- Hackeng, T. M.; Griffin, J. H.; Dawson, P. E.
- Proceedings of the National Academy of Sciences, Vol. 96, Issue 18
Total Chemical Synthesis of Crambin
journal, February 2004
- Bang, Duhee; Chopra, Neeraj; Kent, Stephen B. H.
- Journal of the American Chemical Society, Vol. 126, Issue 5
Synthesis of Glycoproteins
journal, February 2002
- Davis, Benjamin G.
- Chemical Reviews, Vol. 102, Issue 2
The Cyclization and Polymerization of Bacterially Expressed Proteins Using Modified Self-splicing Inteins
journal, June 1999
- Evans, Thomas C.; Benner, Jack; Xu, Ming-Qun
- Journal of Biological Chemistry, Vol. 274, Issue 26
Chemical Synthesis of Proteins
journal, June 2005
- Nilsson, Bradley L.; Soellner, Matthew B.; Raines, Ronald T.
- Annual Review of Biophysics and Biomolecular Structure, Vol. 34, Issue 1
Accurate protein crystallography at ultra-high resolution: Valence electron distribution in crambin
journal, March 2000
- Jelsch, C.; Teeter, M. M.; Lamzin, V.
- Proceedings of the National Academy of Sciences, Vol. 97, Issue 7
Chemical Protein Synthesis by Solid Phase Ligation of Unprotected Peptide Segments
journal, September 1999
- Canne, Lynne E.; Botti, Paolo; Simon, Reyna J.
- Journal of the American Chemical Society, Vol. 121, Issue 38
Total Chemical Synthesis, Folding, and Assay of a Small Protein on a Water-Compatible Solid Support
journal, May 2006
- Johnson, Erik C. B.; Durek, Thomas; Kent, Stephen B. H.
- Angewandte Chemie International Edition, Vol. 45, Issue 20
In situ neutralization in Boc-chemistry solid phase peptide synthesis: Rapid, high yield assembly of difficult sequences
journal, September 1992
- SCHNölzer, Martina; Alewood, Paul; Jones, Alun
- International Journal of Peptide and Protein Research, Vol. 40, Issue 3-4
HPLC of Peptides and Proteins: Basic Theory and Methodology
book, January 2004
- Aguilar, Marie-Isabel
- HPLC of Peptides and Proteins
Total Chemical Synthesis of a Unique Transcription Factor-Related Protein: cMyc-Max
journal, March 1995
- Canne, Lynne E.; Ferre- D'Amare, Adrian R.; Burley, Stephen K.
- Journal of the American Chemical Society, Vol. 117, Issue 11
Synthesis of a thioester linker precursor for a general preparation of peptide C-terminal thioacids
journal, March 2004
- Gaertner, Hubert; Villain, Matteo; Botti, Paolo
- Tetrahedron Letters, Vol. 45, Issue 10
Total synthesis of cytochrome b562 by native chemical ligation using a removable auxiliary
journal, June 2001
- Low, D. W.; Hill, M. G.; Carrasco, M. R.
- Proceedings of the National Academy of Sciences, Vol. 98, Issue 12
2-(4-Nitrophenyl)sulfonylethoxycarbonyl (Nsc) group as a base-labile α-amino protection for solid phase peptide synthesis
journal, October 1994
- Samukov, Vladimir V.; Sabirov, Aydar N.; Pozdnyakov, Pavel I.
- Tetrahedron Letters, Vol. 35, Issue 42
Toward Fully Synthetic Glycoproteins by Ultimately Convergent Routes: A Solution to a Long-Standing Problem
journal, June 2004
- Warren, J. David; Miller, Justin S.; Keding, Stacy J.
- Journal of the American Chemical Society, Vol. 126, Issue 21
His6 tag-assisted chemical protein synthesis
journal, March 2005
- Bang, D.; Kent, S. B. H.
- Proceedings of the National Academy of Sciences, Vol. 102, Issue 14
Synthesis and Application of Unprotected Cyclic Peptides as Building Blocks for Peptide Dendrimers
journal, March 1997
- Zhang, Lianshan; Tam, James P.
- Journal of the American Chemical Society, Vol. 119, Issue 10
Protein arrays: The current state-of-the-art
journal, January 2003
- Cutler, Paul
- PROTEOMICS, Vol. 3, Issue 1
Synthesis of proteins by native chemical ligation
journal, November 1994
- Dawson, P.; Muir, T.; Clark-Lewis, I.
- Science, Vol. 266, Issue 5186
Chemical Ligation of Multiple Peptide Fragments Using a New Protection Strategy
book, January 2001
- Villain, Matteo; Vizzavona, Jean; Gaertner, Hubert
- Peptides: The Wave of the Future
Design and Chemical Synthesis of a Homogeneous Polymer-Modified Erythropoiesis Protein
journal, February 2003
- Kochendoerfer, Gerd G.; Chen, Shiah-Yun; Mao, Feng
- Science, Vol. 299, Issue 5608, p. 884-887
[13] Protein synthesis by chemical ligation of unprotected peptides in aqueous solution
book, January 1997
- Muir, Tom W.; Dawson, Philip E.; Kent, Stephen B. H.
- Solid-Phase Peptide Synthesis
Synthetic glycopeptides and glycoproteins as tools for biology
journal, January 2005
- Pratt, Matthew R.; Bertozzi, Carolyn R.
- Chemical Society Reviews, Vol. 34, Issue 1
A novel amino protection–deprotection procedure and its application in solid phase peptide synthesis
journal, January 1993
- Bycroft, Barrie W.; Chan, Weng C.; Chhabra, Siri Ram
- J. Chem. Soc., Chem. Commun., Issue 9
Total Chemical Synthesis and X-ray Crystal Structure of a Protein Diastereomer: [D-Gln 35]Ubiquitin
journal, June 2005
- Bang, Duhee; Makhatadze, George I.; Tereshko, Valentina
- Angewandte Chemie International Edition, Vol. 44, Issue 25
Semisynthesis of Proteins by Expressed Protein Ligation
journal, June 2003
- Muir, Tom W.
- Annual Review of Biochemistry, Vol. 72, Issue 1