Energy‐resolved HCD fragmentation of daunorubicin‐peptide conjugates

Majidi, L.; Szabó, Dániel; Dókus, Levente Endre; Steckel, Arnold; Mező, Gábor; Schlosser, Gitta

doi:10.1002/jms.4641

Cited by 2 publications

(8 citation statements)

References 17 publications

(20 reference statements)

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“…Protonated sugar-lost conjugates are marked with [M*+H] + , whereas the subsequent water loss is depicted as [M* • +H] + . These results correlate with our previously published data, where only the protonated sugar and the protonated, but charge-reduced sugar-lost conjugate could be detected in the HCD MS/MS spectrum of a doubly protonated Dau = Aoa-SKAAKN-OH conjugate at 10 eV collision energy using a Thermo Scientific Q Exactive Focus mass spectrometer [15].…”

Section: Hcd Experimentssupporting

confidence: 92%

“…This effect is presumably due to multiple collision and fragmentation events resulting in fewer mass fragments. The same behavior was reported by Macht et al in a comparative study of the LID and CID fragmentation processes for ACTH (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), a structural analog of peptide 4, and other peptides [42].…”

Section: Maldi-tof/tof Experimentssupporting

confidence: 83%

“…The exact same fragmentation pattern characterizes the low collision energy HCD MS/MS spectra of conjugates 5 and 6 (Figure S1B,C). charge-reduced sugar-lost conjugate could be detected in the HCD MS/MS spectrum of a doubly protonated Dau=Aoa-SKAAKN-OH conjugate at 10 eV collision energy using a Thermo Scientific Q Exactive Focus mass spectrometer [15].…”

Section: Hcd Experimentsmentioning

confidence: 99%

“…Significant spontaneous fragmentation of anthracycline containing conjugates during electrospray ionization (ESI) has a negative effect on the quality and reliability of the resulting ESI-MS data, thereby hindering the conduct of mass spectrometric analysis of these compounds [14,15]. Daunomycin consists of a tetracyclic quinoid aglycone and a daunosamine sugar moiety attached to the aglycon part through an O-glycosidic bond.…”

Section: Introductionmentioning

confidence: 99%

“…When the drug moiety is attached via oxime bond to the tumor targeting peptides, the cleavage of the sugar moiety from the daunomycin is the most prominent fragmentation pathway [14]. The same sugar loss fragmentation is pronounced during higher energy collision-induced dissociation (higher-energy C-trap dissociation, HCD) MS/MS analysis, thus suppressing the fragmentations of other types [15]. Consequently, MS and MS/MS analysis of daunomycinbioconjugates results in a complex spectrum containing a mixture of daunomycin related fragments, generally hampering unambiguous assignment, accurate purity estimation and definitive structural identification.…”

Section: Introductionmentioning

confidence: 99%

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Structural Characterization of Daunomycin-Peptide Conjugates by Various Tandem Mass Spectrometric Techniques

Borbély

Pethő

Szabó

et al. 2021

IJMS

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The use of peptide-drug conjugates has generated wide interest as targeted antitumor therapeutics. The anthracycline antibiotic, daunomycin, is a widely used anticancer agent and it is often conjugated to different tumor homing peptides. However, comprehensive analytical characterization of these conjugates via tandem mass spectrometry (MS/MS) is challenging due to the lability of the O-glycosidic bond and the appearance of MS/MS fragment ions with little structural information. Therefore, we aimed to investigate the optimal fragmentation conditions that suppress the prevalent dissociation of the anthracycline drug and provide good sequence coverage. In this study, we comprehensively compared the performance of common fragmentation techniques, such as higher energy collisional dissociation (HCD), electron transfer dissociation (ETD), electron-transfer higher energy collisional dissociation (EThcD) and matrix-assisted laser desorption/ionization–tandem time-of-flight (MALDI-TOF/TOF) activation methods for the structural identification of synthetic daunomycin-peptide conjugates by high-resolution tandem mass spectrometry. Our results showed that peptide backbone fragmentation was inhibited by applying electron-based dissociation methods to conjugates, most possibly due to the “electron predator” effect of the daunomycin. We found that efficient HCD fragmentation was largely influenced by several factors, such as amino acid sequences, charge states and HCD energy. High energy HCD and MALDI-TOF/TOF combined with collision induced dissociation (CID) mode are the methods of choice to unambiguously assign the sequence, localize different conjugation sites and differentiate conjugate isomers.

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Section: Hcd Experimentssupporting

confidence: 92%

Section: Maldi-tof/tof Experimentssupporting

confidence: 83%

Section: Hcd Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Structural Characterization of Daunomycin-Peptide Conjugates by Various Tandem Mass Spectrometric Techniques

Borbély

Pethő

Szabó

et al. 2021

IJMS

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Bioconjugates: A New Class of Therapeutics for Cancer Treatment

Mosaa

Al-Majidi

Bader

et al. 2023

JUBPAS

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Bioconjugates represent a novel class of therapeutics that offer promise in the treatment of cancer. These compounds are formed by combining a targeting molecule, such as an antibody or peptide, with a therapeutic agent, such as a chemotherapy drug or toxin. This approach allows for targeted delivery of the therapeutic agent to cancer cells, minimizing damage to healthy tissues and reducing side effects. Bioconjugates have shown significant potential in preclinical and clinical studies, with several FDA-approved drugs currently available for the treatment of cancer. There are several types of bioconjugates currently being developed for cancer treatment, including antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), and nanoparticle-drug conjugates (NDCs). ADCs are the most well-established type of bioconjugate and have been approved for the treatment of several types of cancer, including breast cancer, lymphoma, and leukemia. PDCs and NDCs are newer classes of bioconjugates that are still in the preclinical and early clinical stages of development. Ongoing research in this field aims to improve the efficacy and safety of bioconjugates and expand their use to a wider range of cancer types. As research in this field continues to advance, we can expect to see even more innovative and effective bioconjugate drugs being developed in the future. These drugs are designed to target specific cancer cells, while leaving healthy cells unharmed, and have the potential to revolutionize cancer treatment. Furthermore, bioconjugates can be tailored to individual patients, allowing for personalized and targeted cancer therapy.

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Energy‐resolved HCD fragmentation of daunorubicin‐peptide conjugates

Cited by 2 publications

References 17 publications

Structural Characterization of Daunomycin-Peptide Conjugates by Various Tandem Mass Spectrometric Techniques

Structural Characterization of Daunomycin-Peptide Conjugates by Various Tandem Mass Spectrometric Techniques

Bioconjugates: A New Class of Therapeutics for Cancer Treatment

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