title: Photochemically re-bridging disulfide bonds and the discovery of a thiomaleimide mediated photodecarboxylation of C-terminal cysteines.
abstract: Described in this work is a novel method for photochemically manipulating peptides and proteins via the installation of cysteine-selective photoactive tags. Thiomaleimides, generated simply by the addition of bromomaleimides to reduced disulfide bonds, undergo [2 + 2] photocycloadditions to reconnect the crosslink between the two cysteine residues. This methodology is demonstrated to enable photoactivation of a peptide by macrocyclisation, and reconnection of the heavy and light chains in an antibody fragment to form thiol stable conjugates. Finally we report on an intriguing thiomaleimide mediated photochemical decarboxylation of C-terminal cysteines, discovered during this study.
authors.affiliation: Department of Chemistry, University College London, 20 Gordon St, London, UK. j.r.baker@ucl.ac.uk.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Richards
authors.forename: Sally A
authors.initials: SA
authors.lastname: Fletcher
authors.forename: Muriel
authors.initials: M
authors.lastname: Nobles
authors.forename: Hanno
authors.initials: H
authors.lastname: Kossen
authors.forename: Lauren
authors.initials: L
authors.lastname: Tedaldi
authors.forename: Vijay
authors.initials: V
authors.lastname: Chudasama
authors.forename: Andrew
authors.initials: A
authors.lastname: Tinker
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
mesh_terms: D003500:Cyclization; D003545:Cysteine / Q000737:chemistry*; D003653:Decarboxylation; D004220:Disulfides / Q000737:chemistry*; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D055668:Photochemical Processes
chemical_list: D004220:Disulfides; D008301:Maleimides; D003545:Cysteine