Seeing the Invisibles: Detection of Peptide Enantiomers, Diastereomers, and Isobaric Ring Formation in Lanthipeptides Using Nanopores

Roderick Corstiaan Abraham Versloot, Patricia Arias-Orozco, Matthijs Jonathan Tadema, Florian Leonardus Rudolfus Lucas, Xinghong Zhao, Siewert J Marrink, Oscar Paul Kuipers, Giovanni Maglia*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

2 Citaten (Scopus)
18 Downloads (Pure)


Mass spectrometry (MS) is widely used in proteomic analysis but cannot differentiate between molecules with the same mass-to-charge ratio. Nanopore technology might provide an alternative method for the rapid and cost-effective analysis and sequencing of proteins. In this study, we demonstrate that nanopore currents can distinguish between diastereomeric and enantiomeric differences in l- and d-peptides, not observed by conventional MS analysis, down to individual d-amino acids in small opioid peptides. Molecular dynamics simulations suggest that similar to chiral chromatography the resolution likely arises from multiple chiral interactions during peptide transport across the nanopore. Additionally, we used nanopore recordings to rapidly assess 4- and 11-amino acid ring formation in lanthipeptides, a process used in the synthesis of pharmaceutical peptides. The cyclization step requires distinguishing between constitutional isomers, which have identical MS signals and typically involve numerous tedious experiments to confirm. Hence, nanopore technology offers new possibilities for the rapid and cost-effective analysis of peptides, including those that cannot be easily differentiated by mass spectrometry.

Originele taal-2English
Pagina's (van-tot)18355-18365
Aantal pagina's11
TijdschriftJournal of the American Chemical Society
Nummer van het tijdschrift33
StatusPublished - 23-aug.-2023

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