Synthesis, Characterization and In Vitro Evaluation of Hybrid Monomeric Peptides Suited for Multimodal Imaging by PET/OI: Extending the Concept of Charge—Cell Binding Correlation
In the context of hybrid multimodal imaging agents for gastrin releasing peptide receptor (GRPR) targeting, a correlation between the net charge and the receptor affinity of the agents was recently found. In particular, a decrease in in vitro GRPR binding affinity was observed in case of an increasi...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/10/989 |
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| author | Marco Maspero Xia Cheng Valeska von Kiedrowski Clelia Dallanoce Björn Wängler Ralph Hübner Carmen Wängler |
| author_facet | Marco Maspero Xia Cheng Valeska von Kiedrowski Clelia Dallanoce Björn Wängler Ralph Hübner Carmen Wängler |
| author_sort | Marco Maspero |
| collection | DOAJ |
| description | In the context of hybrid multimodal imaging agents for gastrin releasing peptide receptor (GRPR) targeting, a correlation between the net charge and the receptor affinity of the agents was recently found. In particular, a decrease in in vitro GRPR binding affinity was observed in case of an increasing number of negative charges for dually labeled GRPR-specific peptide dimers suited for positron emission tomography and optical imaging (PET/OI). This adverse influence of anionic charges could be in part compensated by a higher valency of peptide multimerization. However, it remains unknown whether this adverse effect of anionic charges is limited to peptide multimers or if it is also found or even more pronounced when GRPR-specific peptide monomers are dually labeled with fluorescent dye and chelating agent/radionuclide. Moreover, it would be important to know if this effect is limited to GRPR-specific agents only or if these observations also apply to other dually labeled peptides binding to other receptor types. To address these questions, we synthesized hybrid labels, comprising a chelator, different fluorescent dyes carrying different net charges and a functional group for bioconjugation and introduced them into different peptides, specifically targeting the GRPR, the melanocortin-1 receptor (MC1R) and integrin α<sub>v</sub>β<sub>3</sub>. The synthesized conjugates were evaluated with regard to their chemical, radiochemical, photophysical and receptor affinity properties. It was found that neither the <sup>68</sup>Ga-radiolabeling nor the fluorescence characteristics of the dyes were altered by the conjugation of the MIUs to the peptides. Further, it was confirmed that the net number of anionic charges has a negative effect on the GRPR-binding affinity of the GRPR-targeting MIU-peptide monomer conjugates and that this same effect was also found to the same extent for the other receptor systems studied. |
| first_indexed | 2024-03-10T06:16:58Z |
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| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T06:16:58Z |
| publishDate | 2021-09-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-2549ee71ccbf47aa8559d31628c352652023-11-22T19:35:39ZengMDPI AGPharmaceuticals1424-82472021-09-01141098910.3390/ph14100989Synthesis, Characterization and In Vitro Evaluation of Hybrid Monomeric Peptides Suited for Multimodal Imaging by PET/OI: Extending the Concept of Charge—Cell Binding CorrelationMarco Maspero0Xia Cheng1Valeska von Kiedrowski2Clelia Dallanoce3Björn Wängler4Ralph Hübner5Carmen Wängler6Biomedical Chemistry, Clinic of Radiology and Nuclear Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, GermanyMolecular Imaging and Radiochemistry, Clinic of Radiology and Nuclear Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, GermanyMolecular Imaging and Radiochemistry, Clinic of Radiology and Nuclear Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, GermanyMedicinal Chemistry Section “Pietro Pratesi”, Department of Pharmaceutical Sciences, University of Milan, Via L. Mangiagalli 25, 20133 Milan, ItalyMolecular Imaging and Radiochemistry, Clinic of Radiology and Nuclear Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, GermanyBiomedical Chemistry, Clinic of Radiology and Nuclear Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, GermanyBiomedical Chemistry, Clinic of Radiology and Nuclear Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, GermanyIn the context of hybrid multimodal imaging agents for gastrin releasing peptide receptor (GRPR) targeting, a correlation between the net charge and the receptor affinity of the agents was recently found. In particular, a decrease in in vitro GRPR binding affinity was observed in case of an increasing number of negative charges for dually labeled GRPR-specific peptide dimers suited for positron emission tomography and optical imaging (PET/OI). This adverse influence of anionic charges could be in part compensated by a higher valency of peptide multimerization. However, it remains unknown whether this adverse effect of anionic charges is limited to peptide multimers or if it is also found or even more pronounced when GRPR-specific peptide monomers are dually labeled with fluorescent dye and chelating agent/radionuclide. Moreover, it would be important to know if this effect is limited to GRPR-specific agents only or if these observations also apply to other dually labeled peptides binding to other receptor types. To address these questions, we synthesized hybrid labels, comprising a chelator, different fluorescent dyes carrying different net charges and a functional group for bioconjugation and introduced them into different peptides, specifically targeting the GRPR, the melanocortin-1 receptor (MC1R) and integrin α<sub>v</sub>β<sub>3</sub>. The synthesized conjugates were evaluated with regard to their chemical, radiochemical, photophysical and receptor affinity properties. It was found that neither the <sup>68</sup>Ga-radiolabeling nor the fluorescence characteristics of the dyes were altered by the conjugation of the MIUs to the peptides. Further, it was confirmed that the net number of anionic charges has a negative effect on the GRPR-binding affinity of the GRPR-targeting MIU-peptide monomer conjugates and that this same effect was also found to the same extent for the other receptor systems studied.https://www.mdpi.com/1424-8247/14/10/989multimodal imagingPET/OIGRPRMC1Rα<sub>v</sub>β<sub>3</sub>receptor affinity |
| spellingShingle | Marco Maspero Xia Cheng Valeska von Kiedrowski Clelia Dallanoce Björn Wängler Ralph Hübner Carmen Wängler Synthesis, Characterization and In Vitro Evaluation of Hybrid Monomeric Peptides Suited for Multimodal Imaging by PET/OI: Extending the Concept of Charge—Cell Binding Correlation Pharmaceuticals multimodal imaging PET/OI GRPR MC1R α<sub>v</sub>β<sub>3</sub> receptor affinity |
| title | Synthesis, Characterization and In Vitro Evaluation of Hybrid Monomeric Peptides Suited for Multimodal Imaging by PET/OI: Extending the Concept of Charge—Cell Binding Correlation |
| title_full | Synthesis, Characterization and In Vitro Evaluation of Hybrid Monomeric Peptides Suited for Multimodal Imaging by PET/OI: Extending the Concept of Charge—Cell Binding Correlation |
| title_fullStr | Synthesis, Characterization and In Vitro Evaluation of Hybrid Monomeric Peptides Suited for Multimodal Imaging by PET/OI: Extending the Concept of Charge—Cell Binding Correlation |
| title_full_unstemmed | Synthesis, Characterization and In Vitro Evaluation of Hybrid Monomeric Peptides Suited for Multimodal Imaging by PET/OI: Extending the Concept of Charge—Cell Binding Correlation |
| title_short | Synthesis, Characterization and In Vitro Evaluation of Hybrid Monomeric Peptides Suited for Multimodal Imaging by PET/OI: Extending the Concept of Charge—Cell Binding Correlation |
| title_sort | synthesis characterization and in vitro evaluation of hybrid monomeric peptides suited for multimodal imaging by pet oi extending the concept of charge cell binding correlation |
| topic | multimodal imaging PET/OI GRPR MC1R α<sub>v</sub>β<sub>3</sub> receptor affinity |
| url | https://www.mdpi.com/1424-8247/14/10/989 |
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