Arginine side-chain modification that occurs during copper-catalysed azide–alkyne click reactions resembles an advanced glycation end product

Abstract

Dehydroascorbate is a by-product of copper-catalysed azide-alkyne click (CuAAC) reactions and also forms advanced glycation end products (AGEs) in tissues undergoing oxidative stress. Here we isolate and characterize an arginine-dehydroascorbate adduct formed during CuAAC reactions, investigate strategies for preventing its formation, and propose its biological relevance as an AGE.

Diversity‐Oriented Peptide Stapling: A Third Generation Copper‐Catalysed Azide–Alkyne Cycloaddition Stapling and Functionalisation Strategy

“…Notably,w ed ecided not to work on aw ell-established peptidet arget but to select an ovel and challengingp eptide.A spart of our ongoing interest in Gp rotein-coupled receptors (GPCRs), [19][20][21][22][23] the C-terminal a-helix from the G s protein (Ga s CT)w as selected.A fter inspec-tion of the available X-ray crystallographic data for the G s protein in complex with the b 2 adrenergic receptor (PDB 3SN6), [24] isoleucine 383 and asparagine 390 were selected as suitable positionsfor the introduction of as taple. [26] Moreover,t he sequence contains racemisation prone residues such as aspartic acidand histidine. [26] Moreover,t he sequence contains racemisation prone residues such as aspartic acidand histidine.…”

“…[25] The selected target represents ac hallenging sequence due to the presence of three arginine residues that can be problematic when employing the CuAACr eaction. [26] Moreover,t he sequence contains racemisation prone residues such as aspartic acidand histidine. The required Fmoc-protected azido-amino acids 1-3 were synthesised on multi-gram scale by diazo-transfer reaction (see the Supporting Information).…”

Mannosylated hemagglutinin peptides bind cyanovirin-N independent of disulfide-bonds in complementary binding sites

“…Introducing an azide at C 1 of the carbohydrate initiated copper(I)-catalyzed formation of a triazolelinkage between the peptide and the carbohydrate moiety. 29 While N-linked glycosylation on asparagine is the naturally occurring modication, triazoles are excellent amide bioisosteres 30,31 that have been established as directly accessible bridging moiety in N-linked glycopeptides and N-linked glycoproteins. 32 Acetylated methyl-dimannose formation of the disaccharide and introduction of the azide-functionality in the C 1-a position made this building block available for CuAAC on the solid support with a yield of 20% over 7 steps 57,58 (Fig.…”

Traceless Click-Assisted Native Chemical Ligation Enabled by Protecting Dibenzocyclooctyne from Acid-Mediated Rearrangement with Copper(I)

“…For this purpose, we chose to use strain-promoted alkyne-azide cycloaddition (SPAAC) [72][73] over copper-catalyzed azide-alkyne cycloaddition (CuAAC) [74][75] because SPAAC avoids potential copper-catalyzed oxidation during the click reaction. [67][68] In addition, we wanted to perform one-pot templating and NCL and expected that the presence of copper within NCL conditions may cause side-product formation (e.g., during in situ thioester formation 76 ).…”