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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6720970 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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