Ring-opening cross-metathesis (ROCM) as a novel tool for the ligation of peptides.
The development of ring-opening cross-metathesis (ROCM) as a novel tool for the site-specific ligation of peptide units is reported. The resulting structural units at the site of ligation resulting from ROCM resemble proline as well as other known beta-turn stabilising structural units. ROCM under mild reaction conditions between a variety of peptides bearing a cyclic olefin with amino acids or peptides results in high yields. The peptidic cross-partners for metathesis are equipped with double bonds via the N and the C terminus and the side chain, respectively, to allow the synthesis of linear as well as non-linear and branched peptides. The ligation in this manner succeeds with low catalyst loadings, with no need for any excess of one reaction partner and with a high compatibility with a wide range of functional groups. Furthermore, the stereochemical outcome of the ROCM can easily be controlled by using a Hoveyda-type chiral catalyst. Fluorescence labelling of peptides is possible in the same manner when using a cyclic olefin equipped with a fluorescence marker.
Michaelis
Simon
S
Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 135, 10623 Berlin, Germany.
Blechert
Siegfried
S
D003516:Cycloparaffins / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D008968:Molecular Conformation; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*
D003516:Cycloparaffins; D008024:Ligands; D010456:Peptides, Cyclic