Total chemical synthesis of proteins.

  title={Total chemical synthesis of proteins.},
  author={Stephen B. H. Kent},
  journal={Chemical Society reviews},
  volume={38 2},
  • S. Kent
  • Published 26 January 2009
  • Chemistry, Biology
  • Chemical Society reviews
This tutorial review outlines the modern ligation methods that enable the efficient total chemical synthesis of enzymes and other protein molecules. Key to this success is the chemoselective reaction of unprotected synthetic peptides ('chemical ligation'). Notably, native chemical ligation enables the reaction of two unprotected peptides in aqueous solution at neutral pH to form a single product in near quantitative yield. Full-length synthetic polypeptides are folded to form the defined… 

Chemical protein synthesis: Inventing synthetic methods to decipher how proteins work.

  • S. Kent
  • Chemistry
    Bioorganic & medicinal chemistry
  • 2017

Recent extensions to native chemical ligation for the chemical synthesis of peptides and proteins.

Sequential native peptide ligation strategies for total chemical protein synthesis.

This tutorial review is to present the basic concepts and challenges underlying the design of sequential peptide ligation strategies using solution or solid phase chemistry, with a special emphasis on C-to-N and N- to-C three-segment assembly strategies.

Development of Thiol-Independent Peptide Ligations for Protein Chemical Synthesis

Development of chemoselective peptide ligation methods and strategies has enabled complex proteins to be chemically synthesized. The key components in these effective ligations include tolerating the

Chemical Protein Synthesis by Kinetically Controlled Ligation of Peptide O‐Esters

The development of increasingly efficient and general methods for peptide ligation comprises a central objective to synthesize proteins by sequential ligation of three or more unprotected peptide segments by Kent et al. (KCL).

Serine/threonine ligation for the chemical synthesis of proteins.

Modern extensions of native chemical ligation for chemical protein synthesis.

This chapter details a number of important extensions of the original native chemical ligation manifold, with particular focus on the application of new methods in the total chemical synthesis of proteins.



Synthesis of native proteins by chemical ligation.

The facile access to novel analogs provided by chemical protein synthesis has led to original insights into the molecular basis of protein function in a number of systems.

Total chemical synthesis of enzymes

  • S. Kent
  • Chemistry
    Journal of peptide science : an official publication of the European Peptide Society
  • 2003
The total synthesis, at will, of a wide variety of protein and enzyme molecules is made feasible by modern chemical ligation methods. As Emil Fischer intuitively understood, synthetic access to the

Protein synthesis by native chemical ligation: expanded scope by using straightforward methodology.

A straightforward methodology that has enabled us to rapidly analyze the compatibility of the native chemical ligation strategy for X-Cys ligation sites, where X is any of the 20 naturally occurring amino acids, and shows that all 20 amino acids are suitable for ligation.

Synthesis of peptides and proteins without cysteine residues by native chemical ligation combined with desulfurization.

This approach, which provides a general method to prepare alanyl proteins from their cysteinyl forms, can be used to chemically synthesize a variety of polypeptides, as demonstrated by the total chemical syntheses of the cyclic antibiotic microcin J25, the 56-amino acid streptococcal protein G B1 domain, and a variant of the 110-amINO acid ribonuclease, barnase.

Facile synthesis of homogeneous artificial proteins

One of the compounds made, the covalent structure of which was defined by electrospray mass spectrometry, would seem to be the largest artificial protein ever made, in pure form in good yield, by controlled total synthesis.

Convergent chemical synthesis and high-resolution x-ray structure of human lysozyme

This facile and efficient convergent synthesis scheme will enable preparation of unique chemical analogs of the lyso enzyme molecule and will prove useful in numerous areas of lysozyme research in the future.

Chemical synthesis of proteins in solution.

Development of a novel strategy suitable for the solution synthesis of proteins is described, wherein the entire molecule is assembled from fully protected segments in the size range of about 10

Total synthesis of cytochrome b562 by native chemical ligation using a removable auxiliary

The use of the 1-phenyl-2-mercaptoethyl removable auxiliary reported here will greatly expand the applicability of total protein synthesis by native chemical ligation of unprotected peptide segments.

Expressed protein ligation: a general method for protein engineering.

  • T. MuirD. SondhiP. Cole
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
This work illustrates that expressed protein ligation is a simple and powerful new method in protein engineering to introduce sequences of unnatural amino acids, posttranslational modifications, and biophysical probes into proteins of any size.

Total chemical synthesis and X-ray crystal structure of a protein diastereomer: [D-Gln 35]ubiquitin.

An efficient synthetic route to native ubiquitin and its diastereomer [D-Gln 35]ubiquitin was realized by combining a one-pot native chemical ligation process with protein desulfurization.