biostudies-literatureSeebeck FPNIGMS NIH HHS7150-1https://www.ebi.ac.uk/biostudies/studies/S-EPMC2572134biostudies-literatureUnknown128(22)Dehydroalanine is a nonproteinogenic amino acid, but it is a component of a wide variety of natural products with therapeutic activities. Indeed, this alpha,beta-unsaturated residue is a highly versatile building block due to its rigidifying effect on peptide backbones and its electrophilicity which allows site-specific thiol ligations of peptides with small molecules or proteins. To harness such versatility in genetically encoded, combinatorial peptide libraries, we report a simple and robust method for the ribosomal synthesis of dehydroalanine-containing peptides. Selenalysine, a selenium-containing lysine analogue, was recruited as a masked dehydroalanine equivalent. This residue is efficiently incorporated by a reconstituted Escherichia coli translation system at high fidelity and effiJournal of the American Chemical SocietyRibosomal synthesis of dehydroalanine-containing peptides.PMC2572134F32 GM074505-02F32 GM074505GM 074505-02Seebeck FPSzostak JWfalseRibosomal synthesis of dehydroalanine-containing peptides.Dehydroalanine is a nonproteinogenic amino acid, but it is a component of a wide variety of natural products with therapeutic activities. Indeed, this alpha,beta-unsaturated residue is a highly versatile building block due to its rigidifying effect on peptide backbones and its electrophilicity which allows site-specific thiol ligations of peptides with small molecules or proteins. To harness such versatility in genetically encoded, combinatorial peptide libraries, we report a simple and robust method for the ribosomal synthesis of dehydroalanine-containing peptides. Selenalysine, a selenium-containing lysine analogue, was recruited as a masked dehydroalanine equivalent. This residue is efficiently incorporated by a reconstituted Escherichia coli translation system at high fidelity and effi2006-01-01T00:00:00Z2006 Jun2025-04-22T06:46:49.667Z2019-03-27T00:19:01ZS-EPMC25721341673445410.1021/ja060966w