An insulin with the native sequence but virtually no activity.
The B24-B25 peptide bond of insulin was replaced by an ester bond. To our knowledge this is the first replacement of a main chain atom reported for the hormone. It is meant to eliminate a structurally important H-bond between the imino group of B25 and the carbonyl oxygen of A19, and consequently to enhance detachment of the C-terminal B chain from the underlying A chain. On the basis of independent experimental evidence this very conformational change is believed to be a prerequisite for receptor binding. It was thus anticipated that increased flexibility would increase receptor binding and activity. Intriguingly, porcine [B24-B25 CO-O]insulin (depsi-insulin) and likewise [B24-B25 CO-O]des-(B26-B30)insulin-B25-amide (depsi-DPI-amide) were found to be only 3-4% potent.
Institut für Biochemie, Rheinisch-Westfälische Technische Hochschule Aachen, Germany.
A
A
Wollmer
G
G
Gilge
D
D
Brandenburg
H G
HG
Gattner
D017667:Adipocytes / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002942:Circular Dichroism; D006860:Hydrogen Bonding; D007328:Insulin / Q000737:chemistry* / Q000494:pharmacology; D017433:Protein Structure, Secondary; D011972:Receptor, Insulin / Q000737:chemistry / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013552:Swine
D007328:Insulin; D011972:Receptor, Insulin