Journal ArticleDOI
Fmoc-Based Synthesis of Peptide-αThioesters: Application to the Total Chemical Synthesis of a Glycoprotein by Native Chemical Ligation
Youngsook Shin,Katharine A. Winans,Bradley J. Backes,Stephen B.H. Kent,and Jonathan A. Ellman,Carolyn R. Bertozzi +5 more
TLDR
An extension of the native chemical ligation method to the total synthesis of a glycosylated protein, the antimicrobial O-linked glycoprotein diptericin, by using an alkanesulfonamide “safety-catch” linker to circumvent the incompatibility of glycosidic linkages with Boc chemistry.Abstract:
The technique of native chemical ligation has enabled the total chemical synthesis of proteins with molecular weights far in excess of those achievable by conventional stepwise solid-phase peptide synthesis. The method involves the condensation of two unprotected peptide segments, one bearing a C-terminal αthioester and the other an N-terminal cysteine residue, to afford a protein with a native amide linkage at the site of ligation. Here we report an extension of the native chemical ligation method to the total synthesis of a glycosylated protein, the antimicrobial O-linked glycoprotein diptericin. The major challenge in our synthesis was preparation of a 24-residue glycopeptide-αthioester segment, which was complicated by the incompatibility of glycosidic linkages with Boc chemistry and by the incompatibility of thioesters with Fmoc chemistry. The use of an alkanesulfonamide “safety-catch” linker circumvented this problem and permitted the solid-phase synthesis of the glycopeptide-αthioester using standa...read more
Citations
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Journal ArticleDOI
Synthesis of native proteins by chemical ligation.
TL;DR: 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.
Journal ArticleDOI
Chemoselective Ligation and Modification Strategies for Peptides and Proteins
TL;DR: This Review summarizes recent developments in the field of chemoselective ligation and modification strategies and illustrates their application, with examples ranging from the total synthesis of proteins to the semisynthesis of naturally modified proteins.
Journal ArticleDOI
Semisynthesis of Proteins by Expressed Protein Ligation
TL;DR: In this review, the development of this technology is discussed, its broad application to biological systems, and its possible role in the area of proteomics are discussed.
Journal ArticleDOI
Nonclassical Routes for Amide Bond Formation
TL;DR: The present review offers an overview of nonclassical (e.g., with no pre- or in situ activation of a carboxylic acid partner) approaches for the construction of amide bonds.
Journal ArticleDOI
Glycoprotein synthesis: an update.
TL;DR: Glycoprotein Remodeling (GPR) 152, Enzymatic Formation of the Glycan-Protein/ Peptide Link 153, and enzymatics in Glycan Extension 4.2.1.
References
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Journal ArticleDOI
Biological roles of oligosaccharides: all of the theories are correct
TL;DR: The only common features of the varied functions of oligosaccharides are that they either mediate ‘specific recognition’ events or that they provide ‘modulation’ of biological processes.
PatentDOI
Synthesis of proteins by native chemical ligation
TL;DR: The technique of native chemical ligation is employable for chemically synthesizing full length proteins as discussed by the authors, which are chemically identical to proteins produced by cell free synthesis, and can be refolded and/or oxidized to form native disulfide-containing protein molecules.
Journal ArticleDOI
Solid phase peptide synthesis utilizing 9‐fluorenylmethoxycarbonyl amino acids
Gregg B. Fields,Richard L. Noble +1 more
TL;DR: The great variety of conditions under which Fmoc solid phase peptide synthesis may be carried out represents a truly "orthogonal" scheme, and thus offers many unique opportunities for bioorganic chemistry.