title: Rapid cross-metathesis for reversible protein modifications via chemical access to Se-allyl-selenocysteine in proteins.
abstract: Cross-metathesis (CM) has recently emerged as a viable strategy for protein modification. Here, efficient protein CM has been demonstrated through biomimetic chemical access to Se-allyl-selenocysteine (Seac), a metathesis-reactive amino acid substrate, via dehydroalanine. On-protein reaction kinetics reveal a rapid reaction with rate constants of Seac-mediated-CM comparable or superior to off-protein rates of many current bioconjugations. This use of Se-relayed Seac CM on proteins has now enabled reactions with substrates (allyl GlcNAc, N-allyl acetamide) that were previously not possible for the corresponding sulfur analogue. This CM strategy was applied to histone proteins to install a mimic of acetylated lysine (KAc, an epigenetic marker). The resulting synthetic H3 was successfully recognized by antibody that binds natural H3-K9Ac. Moreover, Cope-type selenoxide elimination allowed this putative marker (and function) to be chemically expunged, regenerating an H3 that can be rewritten to complete a chemically enabled "write (CM)-erase (ox)-rewrite (CM)" cycle.
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
authors.forename: Yuya A
authors.initials: YA
authors.lastname: Lin
authors.forename: Omar
authors.initials: O
authors.lastname: Boutureira
authors.forename: Lukas
authors.initials: L
authors.lastname: Lercher
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Bhushan
authors.forename: Robert S
authors.initials: RS
authors.lastname: Paton
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Davis
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry*; D012643:Selenium / Q000737:chemistry*; D017279:Selenocysteine / Q000737:chemistry*
chemical_list: D000475:Alkenes; D011506:Proteins; D017279:Selenocysteine; D012643:Selenium
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