title: One-step site-specific modification of native proteins with 2-pyridinecarboxyaldehydes.
abstract: The chemical modification of proteins is an enabling technology for many scientific fields, including chemical biology, biophysics, bioengineering and materials science. These methods allow the attachment of strategically selected detection probes, polymers, drug molecules and analysis platforms. However, organic reactions that can proceed under conditions mild enough to maintain biomolecular function are limited. Even more rare are chemical strategies that can target a single site, leading to products with uniform properties and optimal function. We present a versatile method for the selective modification of protein N termini that does not require any genetic engineering of the protein target. This reaction is demonstrated for 12 different proteins, including the soluble domain of the human estrogen receptor. The function of this protein was confirmed through the binding of a fluorescent estrogen mimic, and the modified protein was explored as a prototype for the detection of endocrine-disrupting chemicals in water.
authors.affiliation: Department of Chemistry, University of California-Berkeley, Berkeley, California, USA.
authors.forename: James I
authors.initials: JI
authors.lastname: MacDonald
authors.affiliation: Department of Chemistry, University of California-Berkeley, Berkeley, California, USA.
authors.forename: Henrik K
authors.initials: HK
authors.lastname: Munch
authors.affiliation: Department of Chemistry, University of California-Berkeley, Berkeley, California, USA.
authors.forename: Troy
authors.initials: T
authors.lastname: Moore
authors.affiliation: 1] Department of Chemistry, University of California-Berkeley, Berkeley, California, USA. [2] The Molecular Foundry, Materials Sciences Division, Lawrence Berkeley National Laboratories, Berkeley, California, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Francis
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D019921:Biotinylation; D052244:Endocrine Disruptors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D011960:Receptors, Estrogen / Q000737:chemistry / Q000187:drug effects; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D054852:Small Molecule Libraries
chemical_list: D000447:Aldehydes; D052244:Endocrine Disruptors; D007202:Indicators and Reagents; D010455:Peptides; D011506:Proteins; D011725:Pyridines; D011960:Receptors, Estrogen; D054852:Small Molecule Libraries; C522921:picolinaldehyde; D012259:Ribonuclease, Pancreatic
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