A highly efficient, two-step, one-pot synthetic strategy for amides and peptides was developed by employing ynamides as novel coupling reagents under extremely mild reaction conditions. The ynamides not only are effective for simple amide and dipeptide synthesis but can also be used for peptide segment condensation. Importantly, no racemization was detected during the activation of chiral carboxylic acids. Excellent amidation selectivity toward amino groups in the presence of -OH, -SH, -CONH, ArNH, and the NH of indole was observed, making the protection of these functional groups unnecessary in amide and peptide synthesis.

Highly valuable bioconjugated molecules must be synthesized through efficient, chemoselective chemical modifications of peptides and proteins. Herein, we report the chemoselective modification of peptides and proteins via a reaction between selenocysteine residues and aryl/alkyl radicals. In situ radical generation from hydrazine substrates and copper ions proceeds rapidly in an aqueous buffer at near neutral pH (5–8), providing a variety of Se-modified linear and cyclic peptides and proteins conjugated to aryl and alkyl molecules, and to affinity label tag (biotin). This chemistry opens a new avenue for chemical protein modifications.

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While chemical protein synthesis has granted access to challenging proteins,the synthesis of longer proteins is often limited by lowa bundance or non-strategic placement of cysteine residues,w hicha re essential for native chemical ligations,a sw ell as multiple purification and isolation steps. We describe the one-pot total synthesis of human thiosulfate:glutathione sulfurtransferase (TSTD1). WT-TSTD1 was synthesized in aC -to-N synthetic approachi nvolving multiple NCL reactions,C u II -mediated deprotection of selenazolidine (Sez), and chemoselective deselenization. The seleno-analog Se-TSTD1, in whicht he active site Cys is replaced with selenocysteine,w as also synthesized with ak inetically controlled ligation with an N-to-C synthetic approach. The catalytic activity of the two proteins indicated that Se-TSTD1 possessed only four-fold lower activity than WT-TSTD1, thus suggesting that selenoproteins can have physiologically comparable sulfutransferase activity to their cysteine counterparts.

COMMUNICATION This journal isAn environmental friendly direct oxidative amidation between methylarenes and free amines was developed. The aromatic amide could be prepared efficiently from raw chemicals by employing TBHP as the "green" oxidant with the co-catalysis of TBAI and FeCl 3 in water.