title: Rhodium(II) metallopeptide catalyst design enables fine control in selective functionalization of natural SH3 domains.
abstract: Chemically modified proteins are increasingly important for use in fundamental biophysical studies, chemical biology, therapeutic protein development, and biomaterials. However, chemical methods typically produce heterogeneous labeling and cannot approach the exquisite selectivity of enzymatic reactions. While bioengineered methods are sometimes an option, selective reactions of natural proteins remain an unsolved problem. Here we show that rhodium(II) metallopeptides combine molecular recognition with promiscuous catalytic activity to allow covalent decoration of natural SH3 domains, depending on choice of catalyst but independent of the specific residue present. A metallopeptide catalyst succeeds in modifying a single SH3-containing kinase at endogenous concentrations in prostate cancer (PC-3) cell lysate.
authors: Department of Chemistry, Rice University, Houston, Texas 77005 (USA).
authors: Farrukh
authors: F
authors: Vohidov
authors: Jane M
authors: JM
authors: Coughlin
authors: Zachary T
authors: ZT
authors: Ball
mesh_terms: D002384:Catalysis; D045744:Cell Line, Tumor; D004926:Escherichia coli / Q000737:chemistry; D029968:Escherichia coli Proteins / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D051575:Proto-Oncogene Proteins c-yes / Q000737:chemistry; D012238:Rhodium / Q000737:chemistry*; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry
chemical_list: D029968:Escherichia coli Proteins; D009942:Organometallic Compounds; D010455:Peptides; D012238:Rhodium; D051575:Proto-Oncogene Proteins c-yes; C489834:YES1 protein, human; D019061:src-Family Kinases
keywords: bioorganic chemistry; diazo compounds; homogeneous catalysis; protein modifications; rhodium