title: C-Terminal Modification of Fully Unprotected Peptide Hydrazides via in Situ Generation of Isocyanates.
abstract: A method for chemo- and regioselective conjugation of nucleophiles to fully unprotected peptides and proteins via in situ generation of C-terminal isocyanates is reported. Oxidation of C-terminal peptide hydrazides in aqueous media followed by Curtius rearrangement of acyl azides reliably generates isocyanates, which react with a variety of external nucleophiles, such as hydrazines, hydrazides, aromatic thiols, and hydroxylamines. Multiple peptides and a 53 kDa protein hydrazide were conjugated to different nucleophiles using this reaction.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Vinogradov
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Simon
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Pentelute
mesh_terms: D000595:Amino Acid Sequence; D020650:Combinatorial Chemistry Techniques; D006834:Hydrazines / Q000737:chemistry*; D017953:Isocyanates / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry
chemical_list: D006834:Hydrazines; D017953:Isocyanates; D010455:Peptides; D011506:Proteins; C050632:polypeptide C