Total Chemical Synthesis of Proteins

How to synthesize native and modified proteins in the test tube

With contributions from a panel of experts representing a range of disciplines, Total Chemical Synthesis of Proteins presents a carefully curated collection of synthetic approaches and strategies for the total synthesis of native and modified proteins.

Comprehensive in scope, this important reference explores the three main chemoselective ligation methods for assembling unprotected peptide segments, including native chemical ligation (NCL). It includes information on synthetic strategies for the complex polypeptides that constitute glycoproteins, sulfoproteins, and membrane proteins, as well as their characterization. In addition, important areas of application for total protein synthesis are detailed, such as protein crystallography, protein engineering, and biomedical research. The authors also discuss the synthetic challenges that remain to be addressed. This unmatched resource:

• Contains valuable insights from the pioneers in the field of chemical protein synthesis
• Presents proven synthetic approaches for a range of protein families
• Explores key applications of precisely controlled protein synthesis, including novel diagnostics and therapeutics

Written for organic chemists, biochemists, biotechnologists, and molecular biologists, Total Chemical Synthesis of Proteins provides key knowledge for everyone venturing into the burgeoning field of protein design and synthetic biology.

Ashraf Brik is Professor of Chemistry at the Schulich Faculty of Chemistry in the Technion-Israel Institute of Technology. He received academic degrees from the Ben-Gurion University of the Negev from the Technion-Israel Institute of Technology, completing his Ph.D. in 2001. From 2002 to 2006, he was a Research Associate in the Scripps Research Institute. In 2007, he joined the Department of Chemistry in the Ben-Gurion University of the Negev as an Assistant Professor and was promoted to a Full Professor in 2012. Professor Brik has authored over 110 scientific publications and has received numerous scientific awards, including the 2017 Bruno Award, the Bessel Award of the Humboldt Foundation for 2015, the 11th Hirata Award, Teva Award for Excellence in memory of Eli Hurvitz, the 2013 Tetrahedron Young Investigator Award in Bioorganic and Medicinal Chemistry for and the 2011 Israel Chemical Society prize for Outstanding Young Chemists.

Philip E. Dawson is a Professor in the Department of Chemistry, The Scripps Research Institute in La Jolla, CA, where he is also the Dean of Graduate and Postdoctoral Studies. He received his A.B. (1992) from Washington University, and Ph.D. (1996) from the Scripps Institute under the guidance of Stephen Kent. Following postdoctoral work at Caltech, he returned to Scripps as Assistant Professor in 1997. He has served as President of the American Peptide Society and co-chaired the 22nd American Peptide Symposium and the 2016 GRC. He has published over 150 papers, and has been honored with an Alfred P. Sloan Foundation fellowship, the Vincent du Vigneaud Award, the Max Bergmann Kreis Gold Medal and the Zervas Award.

Lei Liu is a Professor of Chemistry at Tsinghua University. Liu received his B.Sc. in chemistry from University of Science and Technology of China (1995-1999). His Ph.D. was obtained in 2004 from the Chemistry Department of Columbia University. From 2004 to 2007, Liu was a Research Associate in the Scripps Research Institute. In 2007, Liu joined the Department of Chemistry in Tsinghua University at Beijing. Liu is now a Full Professor and vice chair of the Chemistry Department of Tsinghua. Professor Liu has authored over 200 scientific publications and has received scientific awards including the National Natural Science Award and Tan Kah Kee Young Scientist Award.

Characterization of synthetic proteins
Native chemical ligation
N to S acyl shifts in protein synthesis
Hydrazide-based protein synthesis
Chemical ubiquitination
Glycoprotein synthesis
Expediting protein synthesis
Synthesis of membrane proteins
Sugar-assisted ligation in protein synthesis
Protein semisynthesis
Expanding native chemical ligation via novel amino acid derivatives
Oxime ligation
Synthesis of selenoproteins
Purification-free ligations
Controlling segment solubility in large protein synthesis
Total chemical synthesis of proteins in neurodegenerative diseases
Solid phase chemical ligation
Auxiliaries in chemical protein synthesis
Peptide ligations at sterically demanding sites
Protein synthesis applied for backbone protein engineering
Histone synthesis
Cylic peptide and protein synthesis via ligation methods
Synthesis of proteins with post-translational modification mimics
Deciphering protein folding using chemical protein synthesis