Method for making insulin precursors and insulin precursor analogues having improved fermentation yield in yeast
OwnerThomas Borglum Kjeldsen, Svend Ludvigseninventors
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Abstract
Novel insulin precursors and insulin precursor analogs comprising a connecting peptide (mini C-peptide) of preferably up to 15 amino acid residues and comprising at least one Gly are provided. The precursors can be converted into human insulin or a human insulin analog. The precursors will typically have a distance between B27 (atom CG2) and A1 (atom CA) of less than 5 Å.
Claims67
An insulin precursor or insulin precursor analog comprising a connecting peptide (C-peptide) being cleavable from the A and B chains said connecting peptide comprising at least one Gly and wherein the B27 (atom CG2) has a proximity to the A1 (atom CA) of less than 5 Å.
An insulin precursor or insulin precursor analog comprising a connecting peptide (C-peptide) being cleavable from the A and B chains said connecting peptide comprising at least one Gly and a cleavage site enabling cleavage of the peptide bond between the A-chain and the connecting peptide, wherein one Gly is immediately N-terminal to said cleavage site.
An insulin precursor or insulin precursor analog comprising a connecting peptide (C-peptide) being cleavable from the A and B chains said connecting peptide comprising at least one Gly, wherein the connecting peptide is of up to 6 amino acid residues in length.
An insulin precursor or insulin precursor analog comprising a sequence of formula I:
- B(1-27)-X3-X2-X1-Y-A(1-21),
- wherein
- X1 is 1-5 amino acid residues in length and comprises at least one Gly,
- X2 is one of Pro, Lys, Ala, Arg or Pro-Thr at position 29 of the B chain,
- X3 is one of Pro, Asp, Lys, or lie at position 28 of the B chain, and
- Y is Lys or Arg.
An insulin precursor or insulin precursor analog comprising a sequence of formula I:
- B(1-27)-X3-X2-X1-Y-A(1-21),
- wherein
- X1 comprises a Gly immediately N-terminal to Y,
- X2 is one of Pro, Lys, Ala, Arg or Pro-Thr at position 29 of the B chain,
- X3 is one of Pro, Asp, Lys, or Ile at position 28 of the B chain, and
- Y is Lys or Arg.
An insulin precursor or insulin precursor analog comprising a sequence of formula I:
- B(1-27)-X3-X2-X1-Y-A(1-21),
- wherein
- X1 comprises at least one Gly,
- X2 is one of Pro, Lys, Ala, Arg or Pro-Thr at position 29 of the B chain,
- X3 is one of Pro, Asp, Lys, or Ile at position 28 of the B chain, and
- Y is Lys or Arg,
- and wherein the B27 (atom CG2) has a proximity to the A1 (atom CA) of less than 5 Å.
Dependencies are inferred from the claim text.