title: Catalytic protein modification with dirhodium metallopeptides: specificity in designed and natural systems.
abstract: In this study, we present advances in the use of rhodium(II) metallopeptides for protein modification. Site-specific, proximity-driven modification is enabled by the unique combination of peptide-based molecular recognition and a rhodium catalyst capable of modifying a wide range of amino-acid side chains. We explore catalysis based on coiled-coil recognition in detail, providing an understanding of the determinants of specificity and culminating in the demonstration of orthogonal modification of separate proteins in cell lysate. In addition, the concepts of proximity-driven catalysis are extended to include modification of the natural Fyn SH3 domain with metallopeptides based on a known proline-rich peptide ligand. The development of orthogonal catalyst-substrate pairs for modification in lysate, and the extension of these methods to new natural protein domains, highlight the capabilities for new reaction design possible in chemical approaches to site-specific protein modification.
authors.affiliation: Department of Chemistry, Rice University, Houston, Texas 77005, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Farrukh
authors.initials: F
authors.lastname: Vohidov
authors.forename: Jane M
authors.initials: JM
authors.lastname: Coughlin
authors.forename: Loren J
authors.initials: LJ
authors.lastname: Stagg
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Arold
authors.forename: John E
authors.initials: JE
authors.lastname: Ladbury
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Ball
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000737:chemistry / Q000378:metabolism; D012238:Rhodium / Q000737:chemistry* / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D009942:Organometallic Compounds; D010455:Peptides; D011506:Proteins; D012238:Rhodium; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn