NON-STANDARD INSULIN ANALOGUES

摘要

An insulin analogue comprises a B-chain polypeptide containing a cyclohexanylalanine substitution at position B24 and optionally containing additional amino-acid substitutions at positions A8, B28, and/or B29. A proinsulin analogue or single-chain insulin analogue containing a B domain containing a cyclohexanylalanine substitution at position B24 and optionally containing additional amino-acid substitutions at positions A8, B28, and/or B29. The analogue may be an analogue of a mammalian insulin, such as human insulin. A nucleic acid encoding such an insulin analogue is also provided. A method of lowering the blood sugar of a patient comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient. A method of semi-synthesis using an unprotected octapeptide by means of modification of an endogenous tryptic site by non-standard amino-acid substitutions.

主权项

1. An insulin analogue comprising the insulin B-chain polypeptide containing a substitution at a position corresponding to position B29 selected from the group consisting of norleucine, aminobutyric acid, aminopropionic acid, ornithine, diaminobutyric acid, and diaminopropionic acid, wherein the insulin B-chain polypeptide is at least 30 amino acids long.