Selenocysteine-Mediated Native Chemical Ligation

✍ Scribed by Richard Quaderer; Axel Sewing; Donald Hilvert

• Book ID: 101391125
• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: German
• Weight: 108 KB
• Volume: 84
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/1522-2675(20010516)84:5<1197::aid-hlca1197>3.0.co;2-#

✦ Synopsis

C-Terminal peptide thioesters are shown to react efficiently with peptide fragments containing an Nterminal selenocysteine to give selenoproteins. In analogy to the native chemical ligation of thioesters and peptides containing N-terminal cysteines, the selenol presumably attacks the thioester nucleophilically to give a selenoester intermediate that subsequently rearranges to give a native chemical bond. The utility of this procedure was demonstrated by the synthesis of a selenium-containing derivative of bovine pancreatic trypsin inhibitor (BPTI) in which Cys 38 is replaced by selenocysteine. The artificial selenoprotein folds into a conformation similar to that of wild-type BPTI and inhibits trypsin and chymotrypsin with unaltered affinity.