Quaternization of Vinyl/Alkynyl Pyridine Enables Ultrafast Cysteine‐Selective Protein Modification and Charge Modulation

Quaternized vinyl‐ and alkynyl‐pyridine reagents were shown to react in an ultrafast and selective manner with several cysteine‐tagged proteins at near‐stoichiometric quantities. We have demonstrated that this method can effectively create a homogenous antibody–drug conjugate that features a precise drug‐to‐antibody ratio of 2, which was stable in human plasma and retained its specificity towards Her2+ cells. Finally, the developed warhead introduces a +1 charge to the overall net charge of the protein, which enabled us to show that the electrophoretic mobility of the protein may be tuned through the simple attachment of a quaternized vinyl pyridinium reagent at the cysteine residues. We anticipate the generalized use of quaternized vinyl‐ and alkynyl‐pyridine reagents not only for bioconjugation, but also as warheads for covalent inhibition and as tools to profile cysteine reactivity.     

Fourier transform ion cyclotron resonance study of the dehydrogenative polymerization of allene and propyne induced by W+ in the gas phase

A Fourier transform ion cyclotron resonance study of the gas-phase reaction of W⁺ with allene is reported. W⁺ successively dehydrogenates at least nine allene molecules, leading to the formation of a series of WC_3nH ions, with WC₂₇H as the largest product observed after a reaction delay of 40 s. Starting from the third reaction, there is a competition between elimination of H₂ and C₂H₂ at each step. The activation of propyne was also investigated and found to lead to essentially the same sequence as with allene. The reaction of W⁺ with 1,1-d₂-allene and collision-induced dissociation spectra of product ions are used to discuss a plausible mechanism for the formation and structures of some of the species observed.