DataSheet1.PDF
Due to its 4 carbonic acid groups being available for bioconjugation, the cyclen tetraphosphinate chelator DOTPI, 1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetrakis[methylene(2-carboxyethylphosphinic acid)], represents an ideal scaffold for synthesis of tetrameric bioconjugates for labeling with radi...
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ftfrontimediafig:oai:figshare.com:article/6119567 2023-05-15T15:53:03+02:00 DataSheet1.PDF Alexander Wurzer Adrienn Vágner Dávid Horváth Flóra Fellegi Hans-Jürgen Wester Ferenc K. Kálmán Johannes Notni 2018-04-10T04:05:32Z https://doi.org/10.3389/fchem.2018.00107.s001 https://figshare.com/articles/DataSheet1_PDF/6119567 unknown doi:10.3389/fchem.2018.00107.s001 https://figshare.com/articles/DataSheet1_PDF/6119567 CC BY 4.0 CC-BY Biochemistry Environmental Chemistry Geochemistry Organic Chemistry Inorganic Chemistry Nuclear Chemistry Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics) Medical Biochemistry and Metabolomics not elsewhere classified Food Chemistry and Molecular Gastronomy (excl. Wine) Analytical Biochemistry Cell Neurochemistry Enzymes Electroanalytical Chemistry Analytical Chemistry not elsewhere classified Organic Green Chemistry Physical Organic Chemistry Catalysis and Mechanisms of Reactions Environmental Chemistry (incl. Atmospheric Chemistry) Huisgen-reaction potentiometry spectrophotometry phosphinate radiopharmaceuticals endoradiotherapy prostate-specific membrane antigen theranostics Dataset 2018 ftfrontimediafig https://doi.org/10.3389/fchem.2018.00107.s001 2018-04-11T22:57:10Z Due to its 4 carbonic acid groups being available for bioconjugation, the cyclen tetraphosphinate chelator DOTPI, 1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetrakis[methylene(2-carboxyethylphosphinic acid)], represents an ideal scaffold for synthesis of tetrameric bioconjugates for labeling with radiolanthanides, to be applied as endoradiotherapeuticals. We optimized a protocol for bio-orthogonal DOTPI conjugation via Cu(I)-catalyzed Huisgen-cycloaddition of terminal azides and alkynes (CuAAC), based on the building block DOTPI(azide) 4 . A detailed investigation of kinetic properties of Cu(II)-DOTPI complexes aimed at optimization of removal of DOTPI-bound copper by transchelation. Protonation and equilibrium properties of Ca(II)-, Zn(II), and Cu(II)-complexes of DOTPI and its tetra-cyclohexylamide DOTPI(Chx) 4 (a model for DOTPI conjugates) as well as kinetic inertness (transchelation challenge in the presence of 20 to 40-fold excess of EDTA) were investigated by pH-potentiometry and spectrophotometry. Similar stability constants of Ca II -, Zn II , and Cu II -complexes of DOTPI (logK (CaL) = 8.65, logK (ZnL = 15.40, logK (CuL) = 20.30) and DOTPI(Chx) 4 (logK (CaL) = 8.99, logK (ZnL) = 15.13, logK (CuL) = 20.42) were found. Transchelation of Cu(II)-complexes occurs via proton-assisted dissociation, whereafter released Cu(II) is scavenged by EDTA. The corresponding dissociation rates [k d = 25 × 10 −7 and 5 × 10 −7 s −1 for Cu(DOTPI) and Cu(DOTPI(Chx) 4 ), respectively, at pH 4 and 298 K] indicate that conjugation increases the kinetic inertness by a factor of 5. However, demetallation is completed within 4.5 and 7.2 h at pH 2 and 25°C, respectively, indicating that Cu(II) removal after formation of CuAAC can be achieved in an uncomplicated manner by addition of excess H 4 EDTA. For proof-of-principle, tetrameric DOTPI conjugates of the prostate-specific membrane antigen (PSMA) targeting motif Lys-urea-Glu (KuE) were synthesized via CuAAC as well as dibenzo-azacyclooctine (DBCO) based, strain-promoted click ... Dataset Carbonic acid Frontiers: Figshare |
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Open Polar |
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Frontiers: Figshare |
op_collection_id |
ftfrontimediafig |
language |
unknown |
topic |
Biochemistry Environmental Chemistry Geochemistry Organic Chemistry Inorganic Chemistry Nuclear Chemistry Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics) Medical Biochemistry and Metabolomics not elsewhere classified Food Chemistry and Molecular Gastronomy (excl. Wine) Analytical Biochemistry Cell Neurochemistry Enzymes Electroanalytical Chemistry Analytical Chemistry not elsewhere classified Organic Green Chemistry Physical Organic Chemistry Catalysis and Mechanisms of Reactions Environmental Chemistry (incl. Atmospheric Chemistry) Huisgen-reaction potentiometry spectrophotometry phosphinate radiopharmaceuticals endoradiotherapy prostate-specific membrane antigen theranostics |
spellingShingle |
Biochemistry Environmental Chemistry Geochemistry Organic Chemistry Inorganic Chemistry Nuclear Chemistry Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics) Medical Biochemistry and Metabolomics not elsewhere classified Food Chemistry and Molecular Gastronomy (excl. Wine) Analytical Biochemistry Cell Neurochemistry Enzymes Electroanalytical Chemistry Analytical Chemistry not elsewhere classified Organic Green Chemistry Physical Organic Chemistry Catalysis and Mechanisms of Reactions Environmental Chemistry (incl. Atmospheric Chemistry) Huisgen-reaction potentiometry spectrophotometry phosphinate radiopharmaceuticals endoradiotherapy prostate-specific membrane antigen theranostics Alexander Wurzer Adrienn Vágner Dávid Horváth Flóra Fellegi Hans-Jürgen Wester Ferenc K. Kálmán Johannes Notni DataSheet1.PDF |
topic_facet |
Biochemistry Environmental Chemistry Geochemistry Organic Chemistry Inorganic Chemistry Nuclear Chemistry Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics) Medical Biochemistry and Metabolomics not elsewhere classified Food Chemistry and Molecular Gastronomy (excl. Wine) Analytical Biochemistry Cell Neurochemistry Enzymes Electroanalytical Chemistry Analytical Chemistry not elsewhere classified Organic Green Chemistry Physical Organic Chemistry Catalysis and Mechanisms of Reactions Environmental Chemistry (incl. Atmospheric Chemistry) Huisgen-reaction potentiometry spectrophotometry phosphinate radiopharmaceuticals endoradiotherapy prostate-specific membrane antigen theranostics |
description |
Due to its 4 carbonic acid groups being available for bioconjugation, the cyclen tetraphosphinate chelator DOTPI, 1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetrakis[methylene(2-carboxyethylphosphinic acid)], represents an ideal scaffold for synthesis of tetrameric bioconjugates for labeling with radiolanthanides, to be applied as endoradiotherapeuticals. We optimized a protocol for bio-orthogonal DOTPI conjugation via Cu(I)-catalyzed Huisgen-cycloaddition of terminal azides and alkynes (CuAAC), based on the building block DOTPI(azide) 4 . A detailed investigation of kinetic properties of Cu(II)-DOTPI complexes aimed at optimization of removal of DOTPI-bound copper by transchelation. Protonation and equilibrium properties of Ca(II)-, Zn(II), and Cu(II)-complexes of DOTPI and its tetra-cyclohexylamide DOTPI(Chx) 4 (a model for DOTPI conjugates) as well as kinetic inertness (transchelation challenge in the presence of 20 to 40-fold excess of EDTA) were investigated by pH-potentiometry and spectrophotometry. Similar stability constants of Ca II -, Zn II , and Cu II -complexes of DOTPI (logK (CaL) = 8.65, logK (ZnL = 15.40, logK (CuL) = 20.30) and DOTPI(Chx) 4 (logK (CaL) = 8.99, logK (ZnL) = 15.13, logK (CuL) = 20.42) were found. Transchelation of Cu(II)-complexes occurs via proton-assisted dissociation, whereafter released Cu(II) is scavenged by EDTA. The corresponding dissociation rates [k d = 25 × 10 −7 and 5 × 10 −7 s −1 for Cu(DOTPI) and Cu(DOTPI(Chx) 4 ), respectively, at pH 4 and 298 K] indicate that conjugation increases the kinetic inertness by a factor of 5. However, demetallation is completed within 4.5 and 7.2 h at pH 2 and 25°C, respectively, indicating that Cu(II) removal after formation of CuAAC can be achieved in an uncomplicated manner by addition of excess H 4 EDTA. For proof-of-principle, tetrameric DOTPI conjugates of the prostate-specific membrane antigen (PSMA) targeting motif Lys-urea-Glu (KuE) were synthesized via CuAAC as well as dibenzo-azacyclooctine (DBCO) based, strain-promoted click ... |
format |
Dataset |
author |
Alexander Wurzer Adrienn Vágner Dávid Horváth Flóra Fellegi Hans-Jürgen Wester Ferenc K. Kálmán Johannes Notni |
author_facet |
Alexander Wurzer Adrienn Vágner Dávid Horváth Flóra Fellegi Hans-Jürgen Wester Ferenc K. Kálmán Johannes Notni |
author_sort |
Alexander Wurzer |
title |
DataSheet1.PDF |
title_short |
DataSheet1.PDF |
title_full |
DataSheet1.PDF |
title_fullStr |
DataSheet1.PDF |
title_full_unstemmed |
DataSheet1.PDF |
title_sort |
datasheet1.pdf |
publishDate |
2018 |
url |
https://doi.org/10.3389/fchem.2018.00107.s001 https://figshare.com/articles/DataSheet1_PDF/6119567 |
genre |
Carbonic acid |
genre_facet |
Carbonic acid |
op_relation |
doi:10.3389/fchem.2018.00107.s001 https://figshare.com/articles/DataSheet1_PDF/6119567 |
op_rights |
CC BY 4.0 |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.3389/fchem.2018.00107.s001 |
_version_ |
1766388117008285696 |