NEW LIGANDS FOR THE HISB10 Zn2 + INSULIN HEXAMERS IN THE R-CONFORMATION

摘要

The present invention relates to novel ligands for the HisB10 Zn2+ sites of the R-state insulin hexamer having the formula A-B-C-D-X (III), wherein: A is a chemical group which reversibly binds to a HisB10 Zn2+ sites of an insulin hexamer; B is a linker; C is a fragment consisting of 0 to 5 neutral amino acids; D is a fragment comprising 1 to 20 positively charged groups independently selected from amino or guanidino groups; and X is OH, NH2 or a diamino group. The present invention also relates to R-state insulin hexamers comprising such ligands, and aqueous insulin preparations comprising such R-state insulin hexamers.