Reactions of the amide group in acylamino acids and peptides

7 Reactions of the amide group in acylamino acids and peptides 

Hydrolysis of the amide bond is the best-known reaction of this functional group, in the biological context (digestion of proteins by proteinases) as well as in the organic chemical context (aqueous hydrolysis in 6 M hydrochloric acid for 12 h at 120 °C or by dilute alkali). However, the essential role of a catalyst is made clear by the fact that a peptide dissolved in pure water survives unchanged for many months, even under reflux. 

There are numerous protocols for protein hydrolysis, involving minor variants of the standard procedure, that are intended to minimise the destruction of particular amino acids (tryptophan and cysteine/cystine in particular) through the sensitivity of their side-chains to the reaction conditions, especially when access of oxygen is not prevented. Tryptophan largely survives alkaline hydrolysis (but other coded amino acids, particularly serine and threonine, but also arginine and cysteine, do not). 

Partial hydrolysis by aqueous acid is a regioselective amide-cleavage process, although it does not relate to a particular amide bond the most easily hydrolysed amide bond in a polyamide is the one that is most exposed to reagents or otherwise enhanced in its propensity to hydrolysis. Partial hydrolysis was an important feature of the earliest structure determinations for peptides (e.g., by Sanger see Chapter 5), and currently features in a method for mass-spectrometric structure determination of peptides (Section 4.11). The alkylation of the amide bond in peptides, described in Chapter 5, assists mass-spectrometric study through increasing the volatility of peptides. 

---