Insights into the deselenization of selenocysteine into alanine and serine

Abstract

The deselenization of selenocysteine selectively removes the selenol group to give alanine under anaerobic conditions or serine under aerobic conditions (oxygen saturation).

Accessing human selenoproteins through chemical protein synthesis

“…Recently, we (and others) were excited to find that the radical quencher, sodium ascorbate, completely inhibits the undesired deselenization (or desulfurization) reaction that occurs in the presence of TCEP, a commonly used reductant in NCL reactions. 44,68 Therefore, all Sec-NCL reactions for SELM synthesis were performed in a buffer containing both TCEP and sodium ascorbate.…”

“…Under anaerobic conditions, the deselenization 34,44 of SELM(48–145) (U48Sez–A78U–A107U) using TCEP in the presence of DTT was completed in 24 h (Fig. S8†).…”

“…Our SELM synthesis is based on four segments with three sequential Sec-NCL reactions, and utilizes a protected form of Sec, selenazolidine (Sez), 43 as well as a deselenization reaction (Scheme 1) that we and others have recently developed. 34,44,45 The shortest member of the selenoprotein family, SELW, was prepared from two peptide segments with a single Cys-NCL reaction (Scheme 2). …”

One‐Pot Ligation–Oxidative Deselenization at Selenocysteine and Selenocystine

“…[6a] This methodology can also be extended to ligation-deselenization at selenol-derived amino acid residues. [7] Independently, our laboratory [8] and Metanis and co-workers, [9] recently demonstrated that, in the presence of an oxidant to outcompete hydrogen atom abstraction, Sec can be transformed into serine (Ser) at the ligation junction which provides a further expansion of Sec-based ligations. While this oxidative deselenization can be performed using O2 as an oxidant, [8][9] peptide cleavage products were observed on larger peptide targets.…”

“…[7] Independently, our laboratory [8] and Metanis and co-workers, [9] recently demonstrated that, in the presence of an oxidant to outcompete hydrogen atom abstraction, Sec can be transformed into serine (Ser) at the ligation junction which provides a further expansion of Sec-based ligations. While this oxidative deselenization can be performed using O2 as an oxidant, [8][9] peptide cleavage products were observed on larger peptide targets. [8] For this reason, following optimization, we arrived at oxone® as an oxidant that could facilitate clean conversion of Sec to Ser in minutes in the presence of TCEP (Scheme 1B).…”