Revisiting ligation at selenomethionine: Insights into native chemical ligation at selenocysteine and homoselenocysteine

Dardashti, Rebecca Notis; Metanis, Norman

doi:10.1016/j.bmc.2017.05.006

Cited by 14 publications

(16 citation statements)

References 51 publications

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“…To prevent the unwanted subsequent deselenization promoted by TCEP, we introduced the radical quencher sodium ascorbate . Under these conditions, selenol‐mediated ligation times were drastically improved …”

Section: Selenomethionine Ligationmentioning

confidence: 99%

“…Selective methylation of hSec to Sem was confirmed using a trypsin digest. Finally, optimized ligation and methylation conditions were applied in the synthesis of NEDD8(2‐78)(Met50Sem) …”

Section: Selenomethionine Ligationmentioning

confidence: 99%

“…40,41 Under these conditions, selenol-mediated ligation times were drastically improved. 42 We then undertook a methodological study of ligations at cysteine (Cys), homocysteine (hCys), selenocysteine (Sec), and hSec and showed that small variations in side-chain pK a had measurable effects on ligation rates. At pH 7, Cys peptides ligated at a faster rate than their hCys counterparts, which can be explained with Cys's lower pK a (8.3) 43 when compared with that of hCys (8.9).…”

Section: Selenomethionine Ligationmentioning

confidence: 99%

“…Finally, optimized ligation and methylation conditions were applied in the synthesis of NEDD8(2-78)(Met50Sem). 42 FIGURE 2 A, General scheme for the preparation of Se-insulin[C6U A , C11U A ]. B, The crystal structure of Se-insulin[C6U A , C11U A ] (PDB: 6H3M).…”

Section: Selenomethionine Ligationmentioning

confidence: 99%

See 3 more Smart Citations

Miklós Bodanszky Award Lecture: Selective chalcogen chemistry to study protein science

Metanis

Dardashti

Mousa

et al. 2019

Journal of Peptide Science

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In recent decades, chemical protein synthesis and the development of chemoselective reactions—including ligation reactions—have led to significant breakthroughs in protein science. Among them are a better understanding of protein structure‐function relationships, the study of protein posttranslational modifications, exploration of protein design, unnatural amino acid incorporation, and the study of therapeutic proteins and protein folding. Chalcogen chemistry, especially that of sulfur and selenium, is quite rich, and we have witnessed continuous progress in this field in recent years. In this short review, we will instead summarize three stories that we have recently presented on chalcogen chemistry and its impact on protein science, which was presented in the Miklós Bodanszky Award Lecture at the 35th European Peptide Society Meeting in Dublin, Ireland, 26 August 2018.

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Section: Selenomethionine Ligationmentioning

confidence: 99%

“…Selective methylation of hSec to Sem was confirmed using a trypsin digest. Finally, optimized ligation and methylation conditions were applied in the synthesis of NEDD8(2‐78)(Met50Sem) …”

Section: Selenomethionine Ligationmentioning

confidence: 99%

Section: Selenomethionine Ligationmentioning

confidence: 99%

Section: Selenomethionine Ligationmentioning

confidence: 99%

See 2 more Smart Citations

Miklós Bodanszky Award Lecture: Selective chalcogen chemistry to study protein science

Metanis

Dardashti

Mousa

et al. 2019

Journal of Peptide Science

Self Cite

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“…[19b, 32] It is unlikely that the g-position of the selenol contributes to as lower rate of ligation, based on ap reviousr eport indicating that this has no impacto nl igation rate. [33] Instead, a direct comparison of isopeptide ligation in the synthesis of diubiquitin with g-a nd d-thiolysine also showed as lower-thanexpected rate of ligation. [20] In fact, the pK a of the peptide amino groups is likely to blame, as the N-terminal a-amino group of ap eptideh as an average pK a of 7.7, [34] while the eamino group of Lysh as ap K a of 10.5, [35] making it significantly less reactive at pH 7, the optimized pH for NCL.…”

mentioning

confidence: 95%

Selenolysine: A New Tool for Traceless Isopeptide Bond Formation

Dardashti¹,

Kumar²,

Sternisha³

et al. 2019

Preprint

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Despite their biological importance,p ost-translationally modified proteins are notoriously difficult to produce in ahomogeneous fashionb yusing conventionalexpressions ystems. Chemical protein synthesis or semisynthesis offers as olutiont ot his problem;h owever,t raditional strategies often rely on sulfur-based chemistry that is incompatiblew ith the presence of any cysteine residues in the target protein. To overcome these limitations,w e presentt he design and synthesis of g-selenolysine, as elenol-containing form of the commonly modified proteinogenic amino acid, lysine. The utility of g-selenolysine is demonstrated with the traceless ligation of the small ubiquitin-like modifier protein, SUMO-1, to ap eptide segment of human glucokinase.T he resultingp olypeptide is poised for native chemical ligation and chemoselective deselenization in the presence of unprotectedc ysteine residues. Selenolysine's straightforward synthesis and incorporation into synthetic peptidesm arks it as au niversal handlef or conjugating any ubiquitin-like modifying protein to its target.

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Amide‐Forming Ligation Reactions

2019

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One of the long‐standing pursuits of synthetic organic chemists is the development of chemical methods for the synthesis of peptides and proteins as tools for understanding biological processes and providing therapeutic solutions to human diseases. The advent of chemoselective ligation reactions for the chemical synthesis of peptides and proteins has enabled synthetic chemists to realize this long‐held dream. In an amide‐forming ligation reaction, two uniquely placed functional groups within the peptide allow peptide or protein segments to be joined in a chemoselective manner with an amide bond. In this chapter, some of the early methods based on principles of the capture/rearrangement strategy for ligation of peptides are catalogued, followed by some of the most versatile and well‐established contemporary methods for the preparation of linear/cyclic peptides and proteins such as the native chemical ligation (NCL) and the α‐ketoacid–hydroxylamine (KAHA) ligation. The chapter concludes with some of the most promising new generation ligation methods such as the potassium acyltrifluoroborate–hydroxylamine (KAT) ligation. The tremendous progress in the past two decades in the development of several ligation methods that rely on a pair of unique functional groups is set to expand the horizons of fully functional proteins and multi‐protein assemblies that are purely synthetically prepared. Although contemporary ligation reactions do not match the speed and efficiency at which proteins are assembled in biological systems, the repertoire of chemoselective amide‐forming ligation methods has already enabled synthetic protein chemistry to surpass biology in terms of chemical and structural diversity.

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Revisiting ligation at selenomethionine: Insights into native chemical ligation at selenocysteine and homoselenocysteine

Cited by 14 publications

References 51 publications

Miklós Bodanszky Award Lecture: Selective chalcogen chemistry to study protein science

Miklós Bodanszky Award Lecture: Selective chalcogen chemistry to study protein science

Selenolysine: A New Tool for Traceless Isopeptide Bond Formation

Amide‐Forming Ligation Reactions

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