Olefin cross-metathesis on proteins: investigation of allylic chalcogen effects and guiding principles in metathesis partner selection.
Olefin metathesis has recently emerged as a viable reaction for chemical protein modification. The scope and limitations of olefin metathesis in bioconjugation, however, remain unclear. Herein we report an assessment of various factors that contribute to productive cross-metathesis on protein substrates. Sterics, substrate scope, and linker selection are all considered. It was discovered during this investigation that allyl chalcogenides generally enhance the rate of alkene metathesis reactions. Allyl selenides were found to be exceptionally reactive olefin metathesis substrates, enabling a broad range of protein modifications not previously possible. The principles considered in this report are important not only for expanding the repertoire of bioconjugation but also for the application of olefin metathesis in general synthetic endeavors.
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA, UK.
Yuya A
YA
Lin
Justin M
JM
Chalker
Benjamin G
BG
Davis
D000475:Alkenes / Q000737:chemistry*; D001407:Bacillus / Q000201:enzymology; D018011:Chalcogens / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D020860:Subtilisin / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000475:Alkenes; D018011:Chalcogens; D011506:Proteins; D014867:Water; D020860:Subtilisin; D003545:Cysteine