[B22-D-arginine]insulin: synthesis and biological properties.
An analogue of porcine insulin which differs from the native molecule in that the amino-acid residue B22-L-arginine is replaced by its D-enantiomer has been synthesized. The [D ArgB22]B-chain was synthesized by the segment condensation method and purified as the di-S-sulfonate by ion exchange chromatoggraphy on SP-Sephadex at pH 3.5. Combination with native porcine sulfhydryl A-chain gave [DArgB22]insulin which was purified by ion exchange chromatography on SP-Sephadex at pH 4.5 with a linear NaCl gradient. The biological activity of this analogue as measured by glucose oxidation in rat epididymal adipocytes was 2%. Thymidine incorporation into DNA of human fibroblast was 16%. The immunoreactivity using antipork insulin antibody in a double antibody immunoassay was 4%. The receptor-binding affinity as measured by radioreceptor assays was 2% with cultured human fibroblasts and 1% with rat adipocytes. These results suggest that the L-configuration at B22-arginine is essential for retaining the biological, immunological and receptor-binding properties of the hormone.
D000273:Adipose Tissue / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D002918:Chymotrypsin; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D007328:Insulin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D013552:Swine
D007202:Indicators and Reagents; D007328:Insulin; C033049:insulin, adipoyl-Arg(B22)-; C036635:insulin, Arg(B22)-; D002918:Chymotrypsin