Disulfide-Driven Cyclic Peptide Synthesis of Human Endothelin-2 with a Solid-Supported Npys-Cl.

Autor:	Taguchi A; Department of Medicinal Chemistry, School of Pharmacy , Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi , Hachioji , Tokyo 192-0392 , Japan., Kobayashi K; Department of Medicinal Chemistry, School of Pharmacy , Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi , Hachioji , Tokyo 192-0392 , Japan., Cui Y; Department of Medicinal Chemistry, School of Pharmacy , Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi , Hachioji , Tokyo 192-0392 , Japan., Takayama K; Department of Medicinal Chemistry, School of Pharmacy , Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi , Hachioji , Tokyo 192-0392 , Japan., Taniguchi A; Department of Medicinal Chemistry, School of Pharmacy , Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi , Hachioji , Tokyo 192-0392 , Japan., Hayashi Y; Department of Medicinal Chemistry, School of Pharmacy , Tokyo University of Pharmacy and Life Sciences , 1432-1 Horinouchi , Hachioji , Tokyo 192-0392 , Japan.
Jazyk:	angličtina
Zdroj:	The Journal of organic chemistry [J Org Chem] 2020 Feb 07; Vol. 85 (3), pp. 1495-1503. Date of Electronic Publication: 2019 Dec 17.
DOI:	10.1021/acs.joc.9b02362
Abstrakt:	We report here the synthesis of human endothelin-2, a peptide of 21 amino acid residues with two disulfide bonds, based on the novel idea of a disulfide-driven cyclic peptide synthesis (DdCPS). This synthesis has two steps: (1) a one-pot solid-phase disulfide ligation of two different sulfur-containing peptide fragments using an Npys-Cl resin and (2) intramolecular cyclization of the disulfide peptide via amide bond formation using a thioester ligation. Human endothelin-2 was obtained in a total yield of 2.2% with two such DdCPS procedures and subsequent deprotection and HPLC purification. This strategy is the basis of a new solid-phase assisted practical synthesis of cyclic disulfide peptides.
Databáze:	MEDLINE
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