Exchange transamidation

Transamidation and Transesteramidation. Transamidation is the mutual exchange of chain fragments in a polyamide, shown as follows where R, R" and R, R" represent polymer chain fragments of any length. 

Semisynthesis has become a suitable technique for chemical variations of large polypeptides or proteins from natural sources. Human insulin differs from porcine insulin only in position B30, where alanine is the C-terminal B-chain residue of porcine insulin but threonine is the C-terminal of the human insulin B-chain. Among the various ways to obtain human insulin from porcine insulin by protease-catalyzed semisynthesis, the one-step conversion by exchange of the C-terminal alanine B of porcine insulin with a threonine residue seems to be the method of choice. Several proteases, e.g. trypsin, achromobacter protease, and car-boxypeptidase Y, are able to catalyze the conversion and various groups have independently described an essential improvement of the enzymatic semisynthesis of insulin.The Hoechst procedure,which was developed as an industrial process, is described below as an example of a large-scale conversion of porcine insulin to human insulin in kilogram amounts for therapeutic application. Based on this type of transamidation reaction, it is easy to prepare various B30-insulin analogues. 

The NH2 group of carboxamides, particularly if unsubstituted, can be exchanged for residues from other amines, hydrazines, etc. Thus A-formyl-amines are often obtained quite smoothly by heating the amine with form-amide in a vacuum at as low as 70°.1144 Higher carboxamides react analogously at temperatures of 150-200°.1145 Transamidation occurs more readily if the carboxamide is melted with the amine hydrochloride 692,1146 and diacyl-amides, including cyclic dicarboximides such as succinimide and phthalimide are more reactive than simple carboxamides.1147... 

This is evident from the fact that practically no further transamidation occurs after removal of the end groups. The direct exchange reaction... 

Peptide Synthesis in an Exchange Reaction during Hydrolysis (Transamidation and Transpbptidation)... 

The reaction of an initiator with an amide group of the polymer chain, instead of that of the monomer, may result in the breaking of the macromolecule. Intermolecular transamidations can also modify the length of the polyamide chains and may generate cyclic stmctures. These exchange reactions result in a modification of the molar mass distribution. 

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