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Rapid one-pot iterative diselenide-selenoester ligation using a novel coumarin-based photolabile protecting group.

ABSTRACT: The development of an iterative one-pot peptide ligation strategy is described that capitalises on the rapid and efficient nature of the diselenide-selenoester ligation reaction, together with photodeselenisation chemistry. This ligation strategy hinged on the development of a novel photolabile protecting group for the side chain of selenocysteine, namely the 7-diethylamino-3-methyl coumarin (DEAMC) moiety. Deprotection of this DEAMC group can be effected in a mild, reagent-free manner using visible light (λ = 450 nm) without deleterious deselenisation of selenocysteine residues, thus enabling a subsequent ligation reaction without purification. The use of this DEAMC-protected selenocysteine in iterative DSL chemistry is highlighted through the efficient one-pot syntheses of 60- and 80-residue fragments of mucin-1 as well as apolipoprotein CIII in just 2-4 hours.

SUBMITTER: Kambanis L

PROVIDER: S-EPMC8317654 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Rapid one-pot iterative diselenide-selenoester ligation using a novel coumarin-based photolabile protecting group.

Kambanis Lucas L Chisholm Timothy S TS Kulkarni Sameer S SS Payne Richard J RJ

Chemical science 20210629 29

The development of an iterative one-pot peptide ligation strategy is described that capitalises on the rapid and efficient nature of the diselenide-selenoester ligation reaction, together with photodeselenisation chemistry. This ligation strategy hinged on the development of a novel photolabile protecting group for the side chain of selenocysteine, namely the 7-diethylamino-3-methyl coumarin (DEAMC) moiety. Deprotection of this DEAMC group can be effected in a mild, reagent-free manner using vis ...[more]

PMID: 34349969

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