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Electrospray ionization (ESI) enables gentle transfer of biomolecules from solution to vacuum, facilitating the study of biomolecular structure under highly controlled conditions. However, biomolecules are desolvated during the ESI process, and the loss of ionic hydrogen bonds to solvent molecules can drive structural rearrangement, most prominently at solvent-exposed charge sites. Microsolvation reagents can bind to these bare charge sites in ESI mass spectrometry (ESI–MS) experiments, providing alternative intermolecular interaction partners. Previously, 18-crown-6 was shown to be an effective reagent for binding to cationic monoalkylammonium residues. More recently, diserinol isophthalamide (DIP) was reported as an analogous anionic microsolvation reagent, primarily for carboxylate residues of small model peptides. Herein, we expand upon this work to examine the complexation of DIP, 1,1’-(1,2-phenylene)bis(3-phenylurea) (PBP), and triclocarban (TCC) with molecules featuring a terminal or linking phosphate moiety. Specifically, using ESI–MS, we assess the binding of these reagents with dimethyl phosphate (DMP), cyclic adenosine monophosphate (cAMP), dibutyryl cAMP, RNA dinucleotides ApU and CpG, and angiotensin II phosphate (DRVpYIHPF). For DMP, the smallest target molecule, reagents TCC, PBP and DIP showed favorable adduction. However, for larger systems, PBP and TCC showed reduced complexation, which was attributed to steric hindrance from the terminal aromatic moieties of PBP and the limited hydrogen bonding network of TCC. Overall, of the three reagents, DIP showed the most consistent performance for anionic microsolvation of phosphate groups, facilitating future studies of gas-phase biomolecular structure and the effects of microsolvation.
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Examining the Effect of an Anion-Binding Reagent on the Structure of Deprotonated Leucine Enkephalin Using Cryogenic-Ion Infrared Action Spectroscopy
Not AvailableBiomolecular systems feature a complex interaction network comprising numerous intra- and intermolecular interactions. By isolating biomolecules under vacuum conditions, the intricate balance between specific interaction motifs can be characterized with precise control over conditions. In this study, we apply cryogenic-ion infrared action spectroscopy and electronic structure methods to examine the structural changes in the deprotonated form of the model peptide leucine enkephalin (YGGFL) upon complexation with diserinol isophthalamide (DIP), an anion-binding reagent. The low-energy conformer of the uncomplexed, deprotonated peptide ([YGGFL - H]-) adopts a noncanonical turn structure stabilized by intramolecular ionic hydrogen bonding to the C-terminal carboxylate moiety. Despite the favorability of DIP to strongly coordinate with carboxylate residues, we find that the structure of the peptide is largely unaffected by the binding of DIP. Instead, DIP only partially coordinates with the carboxylate moiety and is positioned below the backbone turn of YGGFL to engage in additional hydrogen bonding interactions. These findings underscore the stability of the turn structure and the strong energetic penalty imposed by disruption of this motif even when strong intermolecular coordination is expected.
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- Award ID(s):
- 2212926
- PAR ID:
- 10639764
- Publisher / Repository:
- American Chemical Society
- Date Published:
- Journal Name:
- The Journal of Physical Chemistry A
- Volume:
- 129
- Issue:
- 36
- ISSN:
- 1089-5639
- Page Range / eLocation ID:
- 8303 to 8311
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript
- Journal Article:
- https://doi.org/10.1021/acs.jpca.5c03984
