Synthesis of palmitoyl derivatives of insulin and their biological activities.
In order to improve the lipophilicity of peptides, bovine insulin was chosen for the chemical modification using palmitic acid. The N-hydroxysuccinimide ester of palmitic acid was used for attachment to terminal amino groups, and p-methoxybenzoxycarbonyl azide was used for protection of the glycine-A1 amino terminus. We obtained two purified derivatives of insulin, B1-monopalmitoyl- and B1,B29-dipalmitoyl-insulin, which were confirmed to be more lipophilic than the parent insulin on high-performance liquid chromatography (HPLC). The hypoglycemic effects of both products were measured in rats after intravenous and intramuscular injections. The mono derivative was more active than the di derivative and produced a longer effect duration than the native insulin after intravenous injection. The derivatives were also shown to be less immunoreactive as judged by an enzyme immunoassay.
Hashimoto
M
M
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Takada
K
K
Kiso
Y
Y
Muranishi
S
S
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D008297:Male; D010169:Palmitic Acids / Q000138:chemical synthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D010169:Palmitic Acids