title: [B17-D-leucine]insulin and [B17-norleucine]insulin: synthesis and biological properties.
abstract: The chemical synthesis of two porcine insulin analogues is described. Leucine in position B17 of the native molecule was substituted by its D-enantiomer and by L-norleucine, respectively. Both B-chain derivatives were synthesized by fragment condensation and purified as di-S-sulphonates by gel filtration followed by ion exchange chromatography on SP-Sephadex at pH3. Combination with native sulphhydryl A-chain yielded [DLeuB17]insulin and [NleB17]insulin. Both insulin analogues were isolated by gel filtration followed by ion exchange chromatography on CM-cellulose at pH 4.0. Biological activities of the analogues were determined relative to native pork insulin: 1) glucose oxidation in rat epididymal adipocytes was 6% for [DLeuB17]insulin and 16% for [NleB17]insulin, 2) receptor-binding affinity tested with cultured human fibroblasts and with rat adipocytes was 3% for [DLeuB17]insulin and 26% for [NleB17]insulin, and 3) thymidine incorporation into DNA of human fibroblasts was 35% for [DLeuB17]insulin and 100% for [NleB17]insulin.
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001681:Biological Assay; D004261:DNA Replication / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D007328:Insulin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism
chemical_list: D007202:Indicators and Reagents; D007328:Insulin; C040310:insulin, Nle(B17)-; D011972:Receptor, Insulin