Tailoring peptide conformational space with organic gas modifiers in TIMS-MS

  • Alyssa Garabedian
  • Fenfei Leng
  • Mark E. Ridgeway
  • Melvin A. Park
  • Francisco Fernandez-Lima
Original Research


Recently, we showed the advantages of Trapped Ion Mobility Spectrometry for the study of kinetic intermediates of biomolecules as a function of the starting solvent composition (e.g., organic content and pH) and collisional induced activation. In the present work, we further characterize the influence of the bath composition (e.g., organic content) on the conformational space of an intrinsically disordered, DNA binding peptide: AT-hook 3 (Lys-Arg-Pro-Arg-Gly-Arg-Pro-Arg-Lys-Trp). Results show the dependence of the charge state distribution and mobility profiles by doping the solution and the bath gas with organic modifiers (e.g., methanol and acetone). The high resolving power of the TIMS analyzer allowed the separation of multiple IMS band per charge state, and their relative abundances are described as a function of the experimental conditions. The use of gas modifiers resulted in larger inverse  mobilities, with a direct correlation between the size of the modifier and the 1/K0 differences. Conformational isomer inter-conversion rates were observed as a function of the trapping time. Different from solution experiments, a larger variety of organic gas modifiers can be used to tailor the peptide conformational space, since peptide precipitation is not a problem.


Trapped ion mobility mass spectrometry Intrinsically disordered protein HMGA2 ATHP 



This work was supported by the National Science Foundation Division of Chemistry, under CAREER award CHE-1654274, with co-funding from the Division of Molecular and Cellular Biosciences to F.F.-L. The authors will also like to acknowledge the helpful discussions and technical support from Dr. Mark E. Ridgeway and Dr. Melvin A. Park from Bruker Daltonics Inc. during the development and installation of the custom-built TIMS-TOF MS instrument.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Chemistry and BiochemistryFlorida International UniversityMiamiUSA
  2. 2.Biomolecular Sciences InstituteFlorida International UniversityMiamiUSA
  3. 3.Bruker Daltonics Inc.BillericaUSA

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