title: Reactive trityl derivatives: stabilised carbocation mass-tags for life sciences applications.
abstract: The rational design of novel triarylmethyl (trityl)-based mass tags (MT) for mass-spectrometric (MS) applications is described. We propose a "pK(R+) rule" to correlate the stability of trityl carbocations with their MS performance: trityls with higher pK(R+) values ionise and desorb better. Trityl blocks were synthesised that have high pK(R+) values and are stable in conditions of MS analysis; these MTs can be ionised by matrix as well as irradiation with a 337 nm nitrogen laser. (13)C-Labelled tags were prepared for MS quantitation applications. Moreover, the tags were equipped with a variety of functional groups allowing conjugation with different functionalities within (bio)molecules to enhance the MS characteristics of the latter. The MS behaviour of model polycationic trityl compounds with and without the matrix was studied to reveal that poly-trityl clusters are always singly charged under the (MA)LDI-TOF conditions. Several peptide-trityl conjugates were prepared and comparisons revealed a beneficial effect of trityl tags on the conjugate detection in MS. Trityl compounds containing para-methoxy- and dimethylamine groups, as well as a xanthene fragment, showed considerable enhancement in MS detection of model peptides; thus they are promising tools for proteomic applications. Dimethoxytrityl derivatives allow one to distinguish between Arg- and Lys-containing peptides. Maleimido trityl derivatives are suitable for the efficient derivatisation of thiol-containing peptides in pyridine.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, Moscow, 117997, Russia.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Ustinov
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Shmanai
authors.forename: Kaajal
authors.initials: K
authors.lastname: Patel
authors.forename: Irina A
authors.initials: IA
authors.lastname: Stepanova
authors.forename: Igor A
authors.initials: IA
authors.lastname: Prokhorenko
authors.forename: Irina V
authors.initials: IV
authors.lastname: Astakhova
authors.forename: Andrei D
authors.initials: AD
authors.lastname: Malakhov
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Skorobogatyi
authors.forename: Pablo L
authors.initials: PL
authors.lastname: Bernad
authors.forename: Safraz
authors.initials: S
authors.lastname: Khan
authors.forename: Mona
authors.initials: M
authors.lastname: Shahgholi
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Southern
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Korshun
authors.forename: Mikhail S
authors.initials: MS
authors.lastname: Shchepinov
mesh_terms: D000595:Amino Acid Sequence; D002244:Carbon / Q000737:chemistry*; D013058:Mass Spectrometry; D010455:Peptides / Q000737:chemistry; D014320:Triphenylmethyl Compounds / Q000737:chemistry*
chemical_list: D010455:Peptides; D014320:Triphenylmethyl Compounds; D002244:Carbon