Insulin precursors

C - Chemistry – Metallurgy – 12 – N

Patent

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195/128.2, 195/1

C12N 15/81 (2006.01) C07K 14/62 (2006.01) C12N 15/17 (2006.01) C12P 21/06 (2006.01) A61K 38/00 (2006.01)

Patent

CA 1337976

Insulin precursors characterized by the amino acid sequence B(1-29)-X1-X2-Y2-Y1-A(1-21) wherein B(1-29) are the 29 first amino acid residues of the B chain of human insulin starting from the N-terminus, A(1-21) are the 21 amino acid residues of the A chain of human insulin, X1 represents a peptide bond or one or more arbitrary amino acid residues, X2 represents Glu or Asp, and Y1 and Y2 each represents Lys or Arg, the positions A6 and A11, A7 and B7 and A20 and B19, respectively, are connected through sulphur bridges, and, if desired, one or more of the amino acid residues of the chains B(1-29) and A(1-21) are substituted by another amino acid residue, are provided. The insulin precursors are prepared by culturing a yeast strain transformed with a replicable expression vehicle comprising a DNA sequence encoding an insulin precursor of the above formula in a suitable medium and isolating the insulin precursor thus formed from the culture medium. The insulin precursors can be converted into human insulin or insulin analogues by enzymatic treatment in a manner known per se.

603208

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