Peptide bonds using carbodiimides

The available free carboxyl groups of the DAS—HMS can be linked via a peptide bond to available primary amine groups onto highly antigenic carriers using a carbodiimide (19). The carriers used in this case were bovine semm albumin (BSA) and poly-L-lysine (molecular weight 150,000 to 300,000). The... 

Cyanamide is a relevant molecule in prebiotic chemistry, and it was recently shown that water-ice catalyzes the rearrangement of cyanamide to carbodiimide. Carbodiimide could act as a condensation agent in the assembly of amino acids into peptides. In the peptide synthesis, using substitued carbodiimides as condensation agents, formation of L—L bonds is favored over D—D bonds by a ratio of 6 1. ... 

In addition to DCC and EDC many other aliphatic carbodiimides are used in peptide synthesis. Examples include N-t-butyl-N -methylcarbodiimide (BMC), N-t-butyl-N -ethylcarbodiimide (BEC), N,N -dicyclopentylcarbodiimide andN-cyclohexyl-N -isopropylcarbodiimide (CIC). DCC, diisopropylcarbodiimide, BMC and BEC perform similarly in peptide synthesis. " N-cyclohexyl-N -isopropylcarbodiimide (CIC) is comparable or even better than DCC for mediation of peptide bond formation in sohd phase synthesis. Also, the solubility of the derived urea in dichloromethane is useful in the standard procedure. " ... 

Sheehan and another Nobel laureate Khorana showed independently that the mild carbodiimide mediated synthesis is very useful in the condensation reaction of N-blocked amino acids with a different amino acid to form a peptide bond. The O-blocking of carboxylic acid groups in peptide synthesis with amino nucleophiles, such as glycine esters or amides, " or novel silicon containing protective groups is also mediated by carbodiimides. Likewise, alcohols are protected with 4-benzyloxybutyric acid, using EDC/DMPA. ... 

Sheehan and Hess introduced the use of carbodiimides for the synthesis of peptide bonds. The preparative procedure is simple and easy to perform, and therefore it became the most important coupling method. 

The acyl ureas are the main side products at elevated temperatures, and in order to shift the reaction toward peptide bond formation, temperatures around 0° should be used. Presence of an amino group during the reaction, also reduces the formation of acyl urea. The most commonly used carbodiimide for peptide synthesis performed in organic solvents is... 

The urea formed during the reaction is water soluble and can be extracted with water if the peptide synthesis is performed in organic solvents. It can be removed by dialysis or by gel filtration when used to couple haptens to high molecular weight carriers. In addition to the use of carbodiimides for the direct formation of peptide bonds, they can also be applied for the preparation of active esters, such as hydroxysuccinimide... 

Carbodiimide method, a procedure for peptide bond formation using carbodi-imides, R-N=C=N-R, such as dicyclohexyl carbodiimide (DCC), diisopropyl carbodiimide (DIC) and water-soluble carbodi-imides. The carbodiimide reacts in a one-pot procedure with the carboxylate anion of the carboxy component to form a highly reactive O-acylisourea intermediate. The former reacts immediately with the amino function of the amino component to yield the desired peptide derivative and the urea byproduct. Indeed, a more complex mechanism must be taken into consideration. Unwanted side reactions are racemization via the oxazolone mechanism and formation of the unreactive N-acylurea by base-catalyzed acyl migration from the isourea oxygen to nitrogen. The side reactions can be diminished by preparing the O-acylisourea at 0 °C... 

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