Oxidative Deselenization of Selenocysteine: Applications for Programmed Ligation at Serine

Malins, Lara R.; Mitchell, N. J.; McGowan, Sheena; Payne, Richard J.

doi:10.1002/ange.201504639

Cited by 43 publications

(13 citation statements)

References 71 publications

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“…Otherwise, extensions of native chemical ligation have relied on the use of thiol nucleophiles to form S-acyl isopeptides, which undergo rapid S,N-acyl shifts through small rings. An exception is the use of selenocysteine (23)(24)(25)(26) and peptide-α selenoesters (27,28), which exhibit analogous but heightened reactivity.…”

mentioning

confidence: 99%

Amide-forming chemical ligation via O -acyl hydroxamic acids

Dunkelmann

Hirata

Totaro

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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The facile rearrangement of "-acyl isopeptides" to native peptide bonds via ,-acyl shift is central to the success of native chemical ligation, the widely used approach for protein total synthesis. Proximity-driven amide bond formation via acyl transfer reactions in other contexts has proven generally less effective. Here, we show that under neutral aqueous conditions, "-acyl isopeptides" derived from hydroxy-asparagine [aspartic acid-β-hydroxamic acid; Asp(β-HA)] rearrange to form native peptide bonds via an ,-acyl shift. This process constitutes a rare example of an ,-acyl shift that proceeds rapidly across a medium-size ring (t ∼ 15 min), and takes place in water with minimal interference from hydrolysis. In contrast to serine/threonine or tyrosine, which form -acyl isopeptides only by the use of highly activated acyl donors and appropriate protecting groups in organic solvent, Asp(β-HA) is sufficiently reactive to form-acyl isopeptides by treatment with an unprotected peptide-thioester, at low mM concentration, in water. These findings were applied to an acyl transfer-based chemical ligation strategy, in which an unprotected -terminal Asp(β-HA)-peptide and peptide-thioester react under aqueous conditions to give a ligation product ultimately linked by a native peptide bond.

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mentioning

confidence: 99%

Amide-forming chemical ligation via O -acyl hydroxamic acids

Dunkelmann

Hirata

Totaro

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…In another report, Payne and co‐workers demonstrated that deselenization could proceed by an oxidative pathway involving the addition of TCEP and Oxone, whereby Sec was readily converted into a Ser residue (Scheme ) . Syntheses of Eglin C and Muc‐1 glycoform by this methodology have been reported.…”

Section: Other Ligation Techniquesmentioning

confidence: 99%

Chemical Protein Synthesis by Native Chemical Ligation and Variations Thereof

et al. 2019

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For a long time, the total synthesis of proteins was considered as a “mission impossible” because of the tedious and complex synthetic steps and demanding purification processes. However, with the development of modern synthetic methodologies, many protein syntheses have now been reported. More importantly, through chemical synthesis, desired modifications can be installed to target proteins precisely, which is a major advantage over traditional bio‐synthesis approaches. This review summarizes the techniques developed for protein assembly, including native chemical ligation, Se‐mediated ligation, and a range of other ligation methods. A few synthetic examples, whereby synthetic proteins with desired modifications have been utilized for related biological research, are also included. We believe that chemical synthesis can provide alternative pathways to solve problems that have hitherto proved insurmountable by traditional biological approaches.

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“…Furthermore, the buffers were all sparged with argon for 10 minutes before use in order to remove any dissolved O2, as aerobic deselenization has been reported to cause β-hydroxylation at amino acids. 34,42,43 An initial rDSL reaction was attempted by dissolving lyophilised diselenide oligonucleotide 7 (50 nmol, 1 equiv.) and selenoester peptide 8 (200 nmol, 2 equiv.…”

Section: Rdsl-deselenization For the Preparation Of Pocsmentioning

confidence: 99%