Edrnan degradation

Step 3 Once formed, the thiazolone derivative isornerizes to a more stable phenylthiohydantoin (PTH) derivative, which is isolated and characterized, thereby providing identification of the N-terminal amino acid. The remainder of the peptide (formed in step 2) can be isolated and subjected to a second Edrnan degradation. 

Only the N-tenninal amide bond is broken in the Edrnan degradation the rest of the peptide chain remains intact. It can be isolated and subjected to a second Edrnan procedure to determine its new N terminus. We can proceed along a peptide chain by beginning with the N terminus and determining each anino acid in order. The sequence is given directly by the strorcture of the PTH derivative formed in each successive degradation. 

Refer to Figure 26.2 and propose a mechanism for the final step in the Edrnan degradation—the acid-catalyzed rearrangement of the ATZ derivative to the PTH derivative. 

A major advance was devised by Pehr Edrnan (University of Lund, Sweden) that has become the standard method for N-terminal residue analysis. The Edman degradation is based on the chemistry shown in Figure 27.12. A peptide reacts with phenyl isothiocyanate to give a phenylthiocarbamoyl (PTC) derivative, as shown in the first step. This PTC derivative is then treated with an acid in an anhydrous medium (Edrnan used nitrornethane saturated with hydrogen chloride) to cleave the amide bond between the N-terminal anino acid and the remainder of the peptide. No other peptide bonds are cleaved in this step as amide bond hydrolysis requires water. When the PTC derivative is treated with acid in an anhydrous medium, the sulfur atom of the C=S unit acts as... 

---