Native chemical ligation is a technique for constructing a large peptide from two smaller peptides, a C-terminal thioester peptide and a N-terminal cysteine peptide. This process was developed by Phillip Dawson and Steven Kent at The Scripps Research Institute in 1984, about the same time that inteins were discovered, which is nature's analogous reaction. Peptides (from the Greek πεπτος, digestable), are the family of molecules formed from the linking, in a defined order, of various amino acids. ... Thioesters are compounds resulting from the bonding of sulfur with an acyl group (an alkyl group attached to a carbon-oxygen double bond), with the general formula R-S-CO-R. Some biochemists believe that the thioester bond was critical for the origin of life. ... Cysteine is a naturally occurring hydrophobic amino acid which has a sulfhydryl group and is found in most proteins, however only in small quantities. ... Steven Kent (Stephen B H Kent) is a chemist at the University of Chicago who developed native chemical ligation and also demonstrated the principle that mirror-image amino acids put together to form a protein create a mirror-image protein which, if an enzyme, can catalyze the mirror-image reaction. ... The Scripps Research Institute, in La Jolla, California is home to notable chemists such as K. C. Nicolaou or Peter Schultz, as well as neurobiologist Gerald Edelman, and Nobel Laureates Kurt Wuthrich and K. Barry Sharpless. ... An intein is a segment of a protein that is able to excise itself and rejoin the remaining portions (the exteins) with a peptide bond. ...

Peptides synthesized by native chemical ligation must be handled carefully; the thioester piece cannot be synthesized with a nucleophilic base, thus favoring BOC chemistry. Protecting groups on the N-terminal piece cannot have constituents which release as aldehydes or ketones since these will cap the n-terminal cysteine. For the same reason, acetone should be avoided in general use, particularly prior to lyophilization and in washing glassware. kjhfckjdsvsdv ... A ketone is either the functional group characterized by a carbonyl group linked to two other carbon atoms or a compound that contains this functional group. ... In chemistry, acetone (also known as propanone, dimethyl ketone, 2-propanone, propan-2-one and beta-ketopropane) is the simplest representative of the ketones. ... Freeze drying (also known as Lyophilization) is a dehydration process typically used to preserve a perishable material, or to make the material more convenient for transport. ...

The payoff is that coupling long peptides by this technique in many cases is nearly quantitative and provides synthetic access to proteins otherwise impossible to make, due to length or decoration by posttranslational modification.