title: Water-soluble phosphinothiols for traceless staudinger ligation and integration with expressed protein ligation.
abstract: The traceless Staudinger ligation is an effective means to synthesize an amide bond between two groups of otherwise orthogonal reactivity: a phosphinothioester and an azide. An important application of the Staudinger ligation is in the ligation of peptides at a variety of residues. Here, we demonstrate that the traceless Staudinger ligation can be achieved in water with a water-soluble reagent. Those reagents that provide a high yield of amide product discourage protonation of the nitrogen in the key iminophosphorane intermediate. The most efficacious reagent, bis(p-dimethylaminoethyl)phosphinomethanethiol, mediates the rapid ligation of equimolar substrates in water. This reagent is also able to perform a transthioesterification reaction with the thioester intermediate formed during intein-mediated protein splicing. Hence, the traceless Staudinger ligation can be integrated with expressed protein ligation, extending the reach of modern protein chemistry.
authors: Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors: Annie
authors: A
authors: Tam
authors: Matthew B
authors: MB
authors: Soellner
authors: Ronald T
authors: RT
authors: Raines
mesh_terms: D001386:Azides / Q000737:chemistry*; D001880:Boranes / Q000737:chemistry; D004952:Esters; D007202:Indicators and Reagents; D008024:Ligands; D015394:Molecular Structure; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry; D012995:Solubility; D014867:Water
chemical_list: D001386:Azides; D001880:Boranes; D004952:Esters; D007202:Indicators and Reagents; D008024:Ligands; D009946:Organothiophosphorus Compounds; D010455:Peptides; D011506:Proteins; D014867:Water
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