title: Efficient Covalent Bond Formation in Gas-Phase Peptide-Peptide Ion Complexes with the Photoleucine Stapler.
abstract: Noncovalent complexes of hydrophobic peptides GLLLG and GLLLK with photoleucine (L*) tagged peptides G(L* n L m )K (n = 1,3, m = 2,0) were generated as singly charged ions in the gas phase and probed by photodissociation at 355 nm. Carbene intermediates produced by photodissociative loss of N2 from the L* diazirine rings underwent insertion into X-H bonds of the target peptide moiety, forming covalent adducts with yields reaching 30%. Gas-phase sequencing of the covalent adducts revealed preferred bond formation at the C-terminal residue of the target peptide. Site-selective carbene insertion was achieved by placing the L* residue in different positions along the photopeptide chain, and the residues in the target peptide undergoing carbene insertion were identified by gas-phase ion sequencing that was aided by specific (13)C labeling. Density functional theory calculations indicated that noncovalent binding to GL*L*L*K resulted in substantial changes of the (GLLLK + H)(+) ground state conformation. The peptide moieties in [GL*L*LK + GLLLK + H](+) ion complexes were held together by hydrogen bonds, whereas dispersion interactions of the nonpolar groups were only secondary in ground-state 0 K structures. Born-Oppenheimer molecular dynamics for 100 ps trajectories of several different conformers at the 310 K laboratory temperature showed that noncovalent complexes developed multiple, residue-specific contacts between the diazirine carbons and GLLLK residues. The calculations pointed to the substantial fluidity of the nonpolar side chains in the complexes. Diazirine photochemistry in combination with Born-Oppenheimer molecular dynamics is a promising tool for investigations of peptide-peptide ion interactions in the gas phase. Graphical Abstract ᅟ.
authors.affiliation: Department of Chemistry, University of Washington, Bagley Hall, Box 351700, Seattle, WA, 98195-1700, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Shaffer
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám 2, 16610, Prague, Czech Republic.
authors.forename: Prokopis C
authors.initials: PC
authors.lastname: Andrikopoulos
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám 2, 16610, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Řezáč
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám 2, 16610, Prague, Czech Republic. lubos@uochb.cas.cz.
authors.forename: Lubomír
authors.initials: L
authors.lastname: Rulíšek
authors.affiliation: Department of Chemistry, University of Washington, Bagley Hall, Box 351700, Seattle, WA, 98195-1700, USA. turecek@chem.washington.edu.
authors.forename: František
authors.initials: F
authors.lastname: Tureček
mesh_terms: D003978:Diazomethane / Q000737:chemistry; D005740:Gases / Q000737:chemistry; D006860:Hydrogen Bonding; D007477:Ions / Q000737:chemistry; D007930:Leucine / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D010782:Photolysis
chemical_list: D005740:Gases; D007477:Ions; D010455:Peptides; D003978:Diazomethane; D007930:Leucine
keywords: Born-Oppenheimer molecular dynamics; Diazirine chromophores; Laser photodissociation; Peptide–peptide ion complexes; Photoleucine
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