Efficient Covalent Bond Formation in Gas-Phase Peptide-Peptide Ion Complexes with the Photoleucine Stapler

0459070 - ÚOCHB 2017 RIV US eng J - Journal Article
Shaffer, C. J. - Andrikopoulos, Prokopis C. - Řezáč, Jan - Rulíšek, Lubomír - Tureček, F.
Efficient Covalent Bond Formation in Gas-Phase Peptide-Peptide Ion Complexes with the Photoleucine Stapler.
Journal of the American Society for Mass Spectrometry. Roč. 27, č. 4 (2016), s. 633-645. ISSN 1044-0305. E-ISSN 1879-1123
R&D Projects: GA ČR(CZ) GA14-31419S; GA ČR GP13-01214P
Institutional support: RVO:61388963
Keywords : peptide-peptide ion complexes * laser photodissociation * diazirine chromophores * photoleucine * Born-Oppenheimer molecular dynamics
Subject RIV: CF - Physical ; Theoretical Chemistry
Impact factor: 2.786, year: 2016

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 N-2 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 C-13 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.
Permanent Link: http://hdl.handle.net/11104/0259337