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Strategy for the synthesis of large peptides: An application to the total synthesis of human parathyroid hormone [hPTH(1–84)]
Authors:T Kimura  M Takai  Y Masui  T Morikawa  S Sakakibara
Abstract:A strategy suitable for the synthesis of larger peptides is proposed. It involves the following four considerations: (1) all of the side-chain functional groups are protected by benzyl-type protective groups; (2) a water-soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide, is used for the fragment-condensation reactions together with 1-hydroxybenzotriazole as the additive; (3) all the protective groups are cleaved simultaneously by the HF method in the final stage of the synthesis; and (4) side products formed are detected and removed by an efficient high-performance liquid chromatography procedure. The usefulness of these procedures is demonstrated taking the synthesis of human parathyroid hormone hPTH(1–84)] as an example.
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