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The chemical synthesis of [Tyr(I) A19 ] and [Tyr(I 2 ) A19 ]insulin (porcine), using the amino-acid derivatives 3-iodotyrosine and 3,5-diiodotyrosine is described. The synthesis of the iodinated -chains were performed by segment condensation in solution using acid labile protecting groups. The hydroxyl groups of Tyr(I) and Tyr(l2) were unprotected. For the temporary protection of the -amino groups of the A-chain segments containing iodinated tyrosines, the 1 -(4-biphenylyl)-l -methylethoxycarbonyl group was selected. After deprotection and sulphitolysis the iodinated -chain tetra-S-sulphonates were purified by ion exchange chromatography on DEAE cellulose at pH 5.6. Reduction to the sulphhydryl form and the combination with native porcine B-chain yielded [Tyr(I) A19 ] and [Tyr(I 2 ) A19 ]insulin (porcine), respectively.Purification of the first product was achieved by gel filtration and of the later by ion exchange chromatography on CM-cellulose at pH 4.5 and gel filtration. The monoiodinated insulin had a biological activity of 24 ± 2% and the diiodinated analogue 2.6 ± 0.2% as determined in an in vitro lipogenesis assay with epidymal adipocytes. Synthesen von [A19-3-Iodtyrosin] und [A19-3,5-Diiodtyrosin]insulin (Schwein)Zusammenfassung: Die chemische Synthese von [Tyr(I) A19 ] und [Tyr(I 2 ) A19 ]Insulin (Schwein) wird beschrieben. Die Darstellung der [Tyr(I) A19 ]-A-Kette und der [Tyr(I 2 ) A19 ]-A-Kette erfolgte durch Segmentkondensation in Lösung unter Anwendung säurelabiler Schutzgruppen. Die Hydroxylfunktionen von 3-Iodtyrosin und 3,5-Diiodtyrosin blieben im Verlaufe der Synthese ungeschützt. Alle A-Kettenfragmente mit iodiertem Tyrosin wurden am N-Terminus durch die l -(4-Biphenylyl)-1 -methylethoxycarbonyl-Gruppe temporär geschützt. Nach der Deblockierung und der Sulfitolyse wurden die iodierten A-Kettentetra-iS-sulfonate durch lonenaustauschchroma-

The Bunte salt derivative was prepared from bovine insulin-A isolated from natural sources, and was purified by chromatography. Natural abundance 40.55 M H z "N NMR spectra were measured in water and dimethyl sulphoxide. The latter solvent gave the best resolution, and 20 of the 22 possible amide nitrogen signals were detected. Several model oligopeptides were also measured and their usefulness for assignments is discussed.

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