Abstract
Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported α-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.
Highlights
Chemical ligation was introduced as a convergent approach to the synthesis of long peptide or protein chains, where the smaller peptides were chemoselectively coupled in aqueous solution
The field of peptide science is steadily growing and this tremendous progression shows the significance of peptides and proteins as therapeutics
All techniques described can be tailored to prepare a variety of peptides and proteins
Summary
Peptide synthetic techniques based on chemical methods have over 100 years of history (Table 1, Scheme 1). In 1881, Theodor Curtius synthesized the first N-protected dipeptide, benzoylglycylglycine, using the azide-coupling method, where the silver salt of glycine was treated with benzoylchloride. Temporary amino-protecting groups had to be developed to overcome synthetic difficulties. The major limitations of SPPS included incomplete coupling and deprotection reactions, accumulation of byproducts, and aggregation of growing peptides [6,7,8]. To overcome the limitations of SPPS, new techniques for the synthesis of proteins have been developed; chemical ligation has been one of the most successful. The O-acyl isopeptide, known as ‘click’ or ‘switch’ peptide, method is useful for the chemical assembly of highly aggregation-prone polypeptides [11].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
