Реферат: An industry-ready approach for the synthesis of terlipressin is developed: the entire peptide chain assembly and subsequent disulfide bond closure are carried out on a polymeric carrier with a specific precaution for the protection of the N-terminal α-amino group. The effect of various factors on the purity of crude disulfide was studied, and the solid-phase cyclization process was optimized. The designed approach has high fidelity and reproducibility and is applicable for a large-scale peptide synthesis (we show it up to 15 g of the pure product). Using molecular modeling, we have found that the state of the N-terminal amino group (free or protected) has a significant influence on the ability of two cysteine side chains to reach each other, paving the way to a rational choice of protecting groups in peptide synthesis.

Библиографическая ссылка: Avdeev D. , Ovchinnikov M.V. , Medvedev M.G. , Molokoedov A.S. , Sidorova M.V.
Formation of a Disulfide Bridge on the Resin during Solid-Phase Synthesis of Terlipressin: Influence of the Boc-Protected and Free N-Terminal Amino Group
Organic Process Research & Development. 2023. V.27. N9. P.1624-1630. DOI: 10.1021/acs.oprd.3c00142 WOS Scopus OpenAlex

Идентификаторы БД:

≡ Web of science:	WOS:001065159200001
≡ Scopus:	2-s2.0-85171631765
≡ OpenAlex:	W4386274806

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