Selenenylsulfide‐Linked Homogeneous Glycopeptides and Glycoproteins: Synthesis of Human “Hepatic Se Metabolite A”

Abstract

Selenium is a critical mammalian trace element found in proteins in the form of selenocysteine (SeCys) or selenomethionine (SeMet), but its role and metabolism are only partially understood. [1][2][3] Early studies [1,2] have surprisingly shown excretion of selenium as selenosugar 1, so-called "hepatic Se metabolite B"; its presence in rats and humans (liver and urine) also suggests a common cross-species excretion mechanism (Scheme 1). These studies implicated 4, so-called "hepatic Se metabolite A", which was neither isolated in pure form nor fully characterized, as the precursor on the basis of MS fragmentation. Selenosugars 2 and 3 have also been detected in urine, but, notably, glutathionyl precursors (e.g., 5) of these trace metabolites have not yet been identified.[3] Indeed, the exact mechanism of selenium metabolism remains unclear, as do the roles of 4 and 5, and the need for authentic standards has recently been emphasized.

Selen und Selenocystein in der Proteinchemie

“…[39] Eine andere Studie nutzte in kreativer Weise die elektrophile Natur der Selensulfidbindung zwischen Sec und 2-Thiol-5-nitropyridin (TNP), um Sec zu modifizieren, anstatt die Reduktion des leicht oxidierbaren Sec vorzunehmen und damit einen nukleophilen Angriff zu initiieren. [41] Diese Zucker-Peptidkomplexe waren im Blutplasma von Ratten bei 37 8 8Cf ür 95 Stunden stabil. Die Methode wird von einer breiten Auswahl reaktiver Aminosäuren toleriert.…”

“…B. zum Selenosulfid-verknüpften Glykosubtilisin (S156C). [41] Diese Zucker-Peptidkomplexe waren im Blutplasma von Ratten bei 37 8 8Cf ür 95 Stunden stabil.…”

Utilizing Selenocysteine for Expressed Protein Ligation and Bioconjugations

“…8,9,12 Moreover, due to its specialized chemistry, Sec can be specifically manipulated while leaving any of the 20 canonical amino acids unaffected. 13–17 Therefore, Sec’s chemical reactivity can be further exploited to specifically label the protein via selenylsulfide (Se-S), diselenide (Se-Se), and selenoether (C-Se-C) bonds, or via conversion to dehydroalanine (Fig. 1).…”

Synthesis of Simple Alkyl-Seleno-Carbohydrates

“…Incorporate the selenium atom in carbohydrates is one way to further this investigations 1 . We planned this work since alkyl glycosides showed antimicrobial activity 2 and organoselenium serves as important therapeutic compounds, including anticancer agents 3 .…”