Oligopeptides Edman degradation

Just as amines add to the C=N double bond of isocyanates giving ureas (Figure 8.9), they add to the C=N double bond of isothiocyanates, producing thioureas. An important example in this regard is the reaction A + Ph-N=C=S —> B of the three-step Edman degradation of oligopeptides (Figure 8.14). 

Fig. 8.14. Edman degradation of polymer-bound oligopeptides. Here, the three-step reaction sequence is shown.

Side Note 8.2. Sequence Determination of Oligopeptides with the Edman Degradation... 

Step 1 of the Edman degradation is the addition of the NH2 group of the N-ter-minal amino acid to the C=N double bond of phenyl isothiocyanate. Step 2 (B —> C) is an intramolecular SN reaction of an S nucleophile on the carboxyl carbon of a pro-tonated amide. It follows the substitution mechanism shown in Figure 6.5. The substitution product C is a heterocyclic derivative of the N-terminal amino acid. The simultaneously formed second reaction product, the oligopeptide D, which has been shortened by one amino acid, is ejected as the leaving group. 

Next, the new oligopeptide D is degraded according to Edman. It then releases its N-terminal amino acid—that is, the second amino acid of the original oligopeptide A counting from its N-terminus—in the form of an analogous heterocycle, and so on. 

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