Total chemical synthesis of polypeptides and proteins: chemistry of ligation techniques and beyond

Peptide ligation chemistry at selenol amino acids

“…Since its inception almost two decades ago, the method has been successfully employed in the synthesis of hundreds of full-length proteins with and without posttranslational modifications (e.g. glycosylation and phosphorylation) and has been the subject of several reviews [7,10,[12][13][14][15][16][17][18][19][20][21][22][23][24]. A number of extensions to the native chemical ligation transformation have also been reported in subsequent years including kinetically controlled ligation reactions [25] and expressed protein ligation, whereby one of the two ligation partners is produced recombinantly [11,[26][27][28].…”

6.11 N-Acylation Reactions of Amines

“…The continued development of peptide-coupling methods now allows for the routine automated synthesis of small-to-moderate-sized peptide fragments, 6 whereas recent developments in native chemical ligation technology enables large complex proteins to be prepared chemically. 7,8 However, despite these impressive achievements, the ACS Green Chemistry Institute has recently voted the area of 'amide formation avoiding poor atom economy reagents' as one of the most important research challenges currently facing organic chemistry. 9 This is because many widely employed amide bond-forming reactions employ relatively expensive reagents have poor atom economy, and generate relatively large amounts of waste.…”

“…A brief overview of reaction protocols that have been developed for carrying out macrolactamization reactions is included, as well as important developments where chiral catalysts and biocatalysts have been used for the kinetic resolution of racemic amines using enantioselective N-acylation protocols. Given the enormous range of literature concerning amide, 8,[11][12][13][14][15][16][17] peptide, 3,[18][19][20][21][22][23][24] and protein synthesis, 7 it has proven necessary to direct interested readers to the many excellent books and reviews available that document this area. Consequently, the authors apologize in advance for being unable to directly cite many of the seminal contributions that have been published in this field and encourage readers to consult the many references cited within the comprehensive reviews referenced herein, as well as the numerous papers that cite them.…”

Postligation-Desulfurization: A General Approach for Chemical Protein Synthesis

“…In the past few years, this strategy has been further expanded to other natural amino acid sites through the ligation of peptides containing synthetic thiol-derived unnatural amino acids and subsequent desulfurization. In this review we focus on the development of postligation-desulfurization strategy and its application in protein synthesis [4,5,7,9,11,40].…”