Hoechst Aktiengesellschaft

501 Hoechst Aktiengesellschaft

Waldemar Wetekam

Eugen Uhlmann

Wolfgang Konig

Joachim Engels

Hubert Mullner

Polypeptides having a carboxamide carboxyl terminal end and a methionine residue, which is optionally bonded to a bacterial protein, on the amino end can be prepared by synthesis by genetic engineering methods of the corresponding polypeptide having at the C terminal end a glycine residue, and conversion of the latter enzymatically into the amino group of the desired carboxamide group. Peptides which have the aminoacid sequence of growth hormone releasing factor, part sequences thereof, or modifications of these peptides, are readily accessible by this means. The synthesis by genetic engineering methods is advantageously carried out via two gene fragments which are synthesized chemically from smaller, single-stranded structural units. The two gene fragments are then linked enzymatically to give the complete gene, which is incorporated into a suitable vector, amplified there, and the peptide is isolated directly or as a fused protein, and is converted enzymatically into the desired amide.

Preparation of polypeptides having an amide carboxyl terminal end

Secretin, which cannot be prepared directly by genetic engineering because of its carboxylic acid carboxyl-terminus, can be obtained by preparing secretylglycine by genetic engineering and then obtaining secretin therefrom by enzymatic conversion of the terminal glycine radical. The gene for the secretylglycine is synthesized chemically from smaller single-stranded units which are linked enzymatically to give the complete gene, incorporated into a suitable vector and amplified therein, after which the peptide is isolated directly or as a fusion protein and, after cyanogen bromide cleavage, is converted enzymatically into secretin.

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Eppstein/Taunus, Germany

Waldemar Wetekam