Advances in Chemical Protein Modification

Synthesis of aminopyrazoles from sydnones and ynamides

“…Inspired by the strain-promoted alkyne azide cycloaddition (SPAAC), [48][49][50][51][52] which is well-known for its efficacy despite its lack of copper, we set out to investigate the synthesis of strained cyclic ynamides as recently conceptualised by Danheiser et al 53 Additionally, it was recently shown that sydnones are suitable substrates for strain-promoted cycloadditions. 54 In four steps the Ntosyl-azacyclohexyne precursor 10 can be prepared with relative D (Scheme 4).…”

Study of Reactions of Two Mannich Bases Derived of 4’-Hydroxychalcones with Glutathione by RP‑TLC, RP‑HPLC and RP‑HPLC‑ESI‑MS Analysis

“…42,49,50 Indeed, positive charged amino acids proximal to a Cys residue increased the Michael reaction rate as the protonation of the N atom in vinyl-substituted pyridine derivatives also promoted higher reactivity towards Cys. 42,49 Based on this findings and how the effect of thiolate concentration overwhelms any other factor on Michael reaction kinetics, it is suggested that protonated amino groups in compounds 3 and 4 can be determinant for their high reactivity with GSH.…”

“…42,49,50 Indeed, positive charged amino acids proximal to a Cys residue increased the Michael reaction rate as the protonation of the N atom in vinyl-substituted pyridine derivatives also promoted higher reactivity towards Cys. 42,49 Based on this findings and how the effect of thiolate concentration overwhelms any other factor on Michael reaction kinetics, it is suggested that protonated amino groups in compounds 3 and 4 can be determinant for their high reactivity with GSH. 49 Since E1cB reaction takes place by a base-induced abstraction of an α-hydrogen unusually acidic by resonance stabilization of the carbanion intermediate (conjugated base), a slower retro-Michael reaction would be observed possibly if compounds 3 and 4 destabilize the enol intermediate rendering more stable GS-3 and GS-4 conjugates.…”

Reactivity of Persulfides Toward Strained Bicyclo[6.1.0]nonyne Derivatives: Relevance to Chemical Tagging of Proteins

“…As a result, they rapidly emerged as useful tools for protein modifications, proteomics or in vivo imaging. 2,3,4 To date, most of the transformations performed with strained alkynes involve dipolar cycloadditions with azide or other dipoles such as nitrile oxides, diazo derivatives or dienes. However, a new reaction engaging strained cycloalkynes was recently introduced to efficiently trap protein sulfenic acids, a reversible cysteine oxidative posttranslational modification (PTM) implicated in redox signaling and serving as a redox sensor for regulating the cell response to oxidative or nitrosative stimuli.…”