Chapter 27: Amino Acids, Peptides and Proteins

Peptide Synthesis : Forming the peptide bond

• Trying to form the amide by simply reacting the amine and the carboxylic acid is not very effective.
• In order to facilitate the process, a coupling reagent can be used to activate the process.
• A common coupling agent is N,N'-dicyclohexylcarbodiimide (DCCI) which reacts with the carboxylic acid to form a reactive acylating reagent.

• During the coupling reaction the DCCI is converted to a urea that can be readily removed (e.g. by chromatography)

• An alternative method is to use a reactive ester and react it with the amine via a typical nucleophilic acyl substitution reaction.

• A important method of peptide synthesis, the Merrifield Method, (Nobel Prize 1984) involves attaching the initial amino acid to an unreactive polymer and then "growing" the peptide chain while it is still anchored to the polymer.  This methodology makes the removal of excess reagents and by products etc. a simple case of washing them away.  The same type of reactions are those described above are used.

Questions:

• Why don't amines and carboxylic acids react well to give amides ?  
• What better ways are there to make simple amides ?  
• Why is the nitrophenyl ester better in the coupling reaction than a simple methyl ester ?   

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