Polypeptidsynthese an Matrizen

5. Internationales Makromolekulares Symposium

Abstract

Inspite of many progress in preparative peptide chemistry and also after introduction of the solid phase technique by Merrifield and after numerous attempts to improve the purity of products the synthesis of homogenous polypeptides remains still a difficult problem. In the ribosomal protein synthesis chain elongation occurs by insertion at the carboxyl end. Chains can only grow if the A site is occupied by the (correct) amino acid, therefore the formation of trunk sequences is prevented. Amino acids activated on a second phase (like in nature) were formerly used for peptide synthesis by aminolysis with amino acid esters. 

By contrast to preparative peptide chemistry the naturally activated amino acids need no N-protection. Free aminoacyl mercaptanes have been synthesized and used for peptide synthesis many years ago in the authors laboratory. The same principle has now been discovered essentially by F.Lipmanns group to serve for the synthesis of certain polypeptides in microorganisms (gramicidines, tyrocidine, bacitracin). In these processes the amino acids are bound to SH groups of a multienzyme template and brought together by the help of 4'-phosphopantheteine as a transporting swinging arm. – α-Amanitin, a cyclic peptide of fungal origin is an inhibitor of microsomal protein synthesis. Its point of attack is the DNA dependent RNA polymerase II (B), which is responsible for the synthesis of precursors of messenger-RNA’s.