Aspart Proinsulin Compositions and Methods of Producing Aspart Insulin Analogs

摘要

Aspart modified proinsulin sequences that have a modified C-peptide amino acid and/or nucleic acid modification for producing aspart insulin analogs are provided. Highly efficient processes for preparing the aspart insulin analogs and improved preparations containing the aspart insulin analogs prepared according to the methods described herein are also provided.

主权项

1. A composition comprising a modified aspart proinsulin peptide having the formula R1-(B1-B26)-B27-B28-B29-B30-R2-R3-X-R4-R5-(A1-A20)-A21-R6, wherein
R1 is a tag sequence comprising one or more amino acids or R1 is absent with an Arg or Lys present prior to the start of the B chain; (B1-B26) and (A1-A20) comprise amino acid sequences of native human insulin; B27 is Thr, Asp, or Glu; B28 is Asp, Glu, or Pro; B29 is Lys, or Pro; B30 is Ala, Thr, or is absent; R2, R3 and R5 are Arg; R4 is any amino acid other than Gly, Lys or Arg or is absent; X comprises one or more amino acids or is absent, provided that X does not comprise a C-terminal Gly, Lys, or Arg when R4 is absent; A21 is Asn, Gly, Ala, Val, Leu, Ile, Pro, Phe, Trp, Met, Ser, Thr, Tyr, Asp, or Glu; and R6 is a tag sequence comprising one or more amino acids or R6 is absent.