Supramolecular Enhancement of Protein Analysis via the Recognition of Phenylalanine with Cucurbit[7]uril

Jong Wha Lee, Min Hyeon Shin, William Mobley, Adam R. Urbach, Hugh I. Kim

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Mass spectrometry (MS)-based analysis using enzymatic digestion is widely used for protein sequencing and characterization. The large number of peptides generated from proteolysis, however, suppresses the signal of peptides with low ionization efficiency, thus precluding their observation and analysis. This study describes a technique for improved analysis of peptic peptides by adding the synthetic receptor cucurbit[7]uril (CB[7]), which binds selectively to peptides with N-terminal aromatic residues. Capturing the N-terminal phenylalanine (Phe) of peptides using CB[7] enhances the peptide abundances both in electrospray ionization MS and in matrix-assisted laser desorption ionization MS. Moreover, collision-induced dissociation (CID) of the CB[7]·peptide complex ions generates b- and y-type fragment ions with higher sequence coverage than those generated with uncomplexed peptides. The signal enhancement mediated by CB[7] is attributed to an increase in the peptide proton affinities upon CB[7] complexation. The mechanistic details of the fragmentation process are discussed on the basis of the structures of the complex ions obtained from ion mobility (IM) measurements and molecular modeling. This study demonstrates a novel and powerful approach to the enhancement of protein and peptide analysis using a synthetic receptor, without the need for new instrumentation, chemical modifications, or specialized sample preparation. The simplicity and potential generality of this technique should provide a valuable asset in the toolbox of routine protein and peptide analysis.

Original languageEnglish
Pages (from-to)15322-15329
Number of pages8
JournalJournal of the American Chemical Society
Volume137
Issue number48
DOIs
Publication statusPublished - 2015 Dec 9

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Phenylalanine
Peptides
Proteins
Artificial Receptors
Ions
Mass spectrometry
Ionization
Digestion
cucurbit(7)uril
Proteolysis
Electrospray ionization
Molecular modeling
Electrospray Ionization Mass Spectrometry
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Protein Sequence Analysis
Chemical modification
Protein Sorting Signals
Complexation
Protons
Desorption

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Supramolecular Enhancement of Protein Analysis via the Recognition of Phenylalanine with Cucurbit[7]uril. / Lee, Jong Wha; Shin, Min Hyeon; Mobley, William; Urbach, Adam R.; Kim, Hugh I.

In: Journal of the American Chemical Society, Vol. 137, No. 48, 09.12.2015, p. 15322-15329.

Research output: Contribution to journalArticle

Lee, Jong Wha ; Shin, Min Hyeon ; Mobley, William ; Urbach, Adam R. ; Kim, Hugh I. / Supramolecular Enhancement of Protein Analysis via the Recognition of Phenylalanine with Cucurbit[7]uril. In: Journal of the American Chemical Society. 2015 ; Vol. 137, No. 48. pp. 15322-15329.
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