Preparation and properties of citraconylinsulins.
Acylation of insulin with citraconic anhydride was studied at different pH values. The controlled acylation at pH 8.5 and 7 yielded mainly A1-citraconylinsulin (41%) and A1,B1-dicitraconylinsulin (39%), respectively. Acylation with excess reagent at pH 5.6, followed by partial deblocking at pH 5 for 30 min and 17 h, led mainly to A1,B1-dicitraconylinsulin (51%) and B1-citraconylinsulin (40%), respectively. The order of the deblocking rates for the three citraconyl groups at pH 3.5 and 5 was B29 much greater than A1 greater than B1. The biological activity of citraconyl derivatives: A1-citraconyl, B1-citraconyl and A1,B1-dicitraconylinsulin were found to be 15%, 100% and 15% (in vitro fat cell assay) and 46%, 78% and 48% (in mouse convulsion assay), respectively. In a double insulin immunoassay these derivatives had 40%, 75% and 30% immunoreactivity, respectively.
D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001681:Biological Assay; D007202:Indicators and Reagents; D007328:Insulin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008722:Methods; D051379:Mice; D012640:Seizures / Q000139:chemically induced; D013329:Structure-Activity Relationship; D013552:Swine
D007202:Indicators and Reagents; D007328:Insulin; C036640:insulin, citraconyl-