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Overcharging Effect in Electrospray Ionization Mass Spectra of Daunomycin-Tuftsin Bioconjugates

Peptide-based small molecule drug conjugates for targeted tumor therapy are currently in the focus of intensive research. Anthracyclines, like daunomycin, are commonly used anticancer drug molecules and are also often applied in peptide-drug conjugates. However, lability of the O-glycosidic bond dur...

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Autores principales: Pethő, Lilla, Mező, Gábor, Schlosser, Gitta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720970/
https://www.ncbi.nlm.nih.gov/pubmed/31426442
http://dx.doi.org/10.3390/molecules24162981
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author Pethő, Lilla
Mező, Gábor
Schlosser, Gitta
author_facet Pethő, Lilla
Mező, Gábor
Schlosser, Gitta
author_sort Pethő, Lilla
collection PubMed
description Peptide-based small molecule drug conjugates for targeted tumor therapy are currently in the focus of intensive research. Anthracyclines, like daunomycin, are commonly used anticancer drug molecules and are also often applied in peptide-drug conjugates. However, lability of the O-glycosidic bond during electrospray ionization mass spectrometric analysis hinders the analytical characterization of the constructs. “Overprotonation” can occur if daunomycin is linked to positively charged peptide carriers, like tuftsin derivatives. In these molecules, the high number of positive charges enhances the in-source fragmentation significantly, leading to complex mass spectra composed of mainly fragment ions. Therefore, we investigated different novel tuftsin-daunomycin conjugates to find an appropriate condition for mass spectrometric detection. Our results showed that shifting the charge states to lower charges helped to keep ions intact. In this way, a clear spectrum could be obtained containing intact protonated molecules only. Shifting of the protonation states to lower charges could be achieved with the use of appropriate neutral volatile buffers and with tuning the ion source parameters.
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spelling pubmed-67209702019-09-10 Overcharging Effect in Electrospray Ionization Mass Spectra of Daunomycin-Tuftsin Bioconjugates Pethő, Lilla Mező, Gábor Schlosser, Gitta Molecules Article Peptide-based small molecule drug conjugates for targeted tumor therapy are currently in the focus of intensive research. Anthracyclines, like daunomycin, are commonly used anticancer drug molecules and are also often applied in peptide-drug conjugates. However, lability of the O-glycosidic bond during electrospray ionization mass spectrometric analysis hinders the analytical characterization of the constructs. “Overprotonation” can occur if daunomycin is linked to positively charged peptide carriers, like tuftsin derivatives. In these molecules, the high number of positive charges enhances the in-source fragmentation significantly, leading to complex mass spectra composed of mainly fragment ions. Therefore, we investigated different novel tuftsin-daunomycin conjugates to find an appropriate condition for mass spectrometric detection. Our results showed that shifting the charge states to lower charges helped to keep ions intact. In this way, a clear spectrum could be obtained containing intact protonated molecules only. Shifting of the protonation states to lower charges could be achieved with the use of appropriate neutral volatile buffers and with tuning the ion source parameters. MDPI 2019-08-16 /pmc/articles/PMC6720970/ /pubmed/31426442 http://dx.doi.org/10.3390/molecules24162981 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pethő, Lilla
Mező, Gábor
Schlosser, Gitta
Overcharging Effect in Electrospray Ionization Mass Spectra of Daunomycin-Tuftsin Bioconjugates
title Overcharging Effect in Electrospray Ionization Mass Spectra of Daunomycin-Tuftsin Bioconjugates
title_full Overcharging Effect in Electrospray Ionization Mass Spectra of Daunomycin-Tuftsin Bioconjugates
title_fullStr Overcharging Effect in Electrospray Ionization Mass Spectra of Daunomycin-Tuftsin Bioconjugates
title_full_unstemmed Overcharging Effect in Electrospray Ionization Mass Spectra of Daunomycin-Tuftsin Bioconjugates
title_short Overcharging Effect in Electrospray Ionization Mass Spectra of Daunomycin-Tuftsin Bioconjugates
title_sort overcharging effect in electrospray ionization mass spectra of daunomycin-tuftsin bioconjugates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720970/
https://www.ncbi.nlm.nih.gov/pubmed/31426442
http://dx.doi.org/10.3390/molecules24162981
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