Chemical synthesis of a homoserine-mutant of the antibacterial, head-to-tail cyclized protein AS-48 by α-ketoacid-hydroxylamine (KAHA) ligation.

Chemical synthesis of a homoserine-mutant of the antibacterial, head-to-tail cyclized protein AS-48 by α-ketoacid–hydroxylamine (KAHA) ligation† †Electronic supplementary information (ESI) available: Experimental procedures, supplementary results, and spectroscopic data for new compounds. See DOI: 10.1039/c7sc00789b Click here for additional data file.

An antibacterial cyclic AS-48 protein was chemically synthesized by a-ketoacid–hydroxylamine (KAHA) ligation. Initial challenges associated with the exceptionally hydrophobic segments arising from the amphiphilic nature of the protein were resolved by the development of bespoke reaction conditions for hydrophobic segments, using hexafluoroisopropanol (HFIP) as a co-solvent. The synthetic protei...

Chemoselective cyclization of unprotected linear peptides by α-ketoacid-hydroxylamine amide-ligation.

Cyclic peptides are important synthetic targets due to their constrained conformation, enhanced metabolic stability and improved bioavailability, which combine to make them promising lead compounds for drug candidates. They are typically synthesized by a multi-step sequence of carefully orchestrated protecting group manipulations and cyclization of side-chain protected linear precursors. In the...

An oxazetidine amino acid for chemical protein synthesis by rapid, serine-forming ligations.

Amide-forming ligation reactions allow the chemical synthesis of proteins by the union of unprotected peptide segments, and enable the preparation of protein derivatives not accessible by expression or bioengineering approaches. The native chemical ligation (NCL) of thioesters and N-terminal cysteines is unquestionably the most successful approach, but is not ideal for all synthetic targets. He...

Chemical methods for peptide and protein production.

Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and n...

Spontaneous head-to-tail cyclization of unprotected linear peptides with the KAHA ligation† †Electronic supplementary information (ESI) available: Experimental procedures and analytical data of all new compounds. See DOI: 10.1039/c5sc01774b Click here for additional data file.