Novel Bifunctional [16]aneS<sub>4</sub>-Derived Chelators for Soft Radiometals
The field of targeted radionuclide therapy is rapidly growing, highlighting the need for wider radionuclide availability. Soft Lewis acid ions, such as radioisotopes of platinum, rhodium and palladium, are particularly underdeveloped. This is due in part to a lack of compatible bifunctional chelator...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/15/4603 |
| _version_ | 1827686414436794368 |
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| author | Natan J. W. Straathof Charlotte B. Magnus Fedor Zhuravlev Andreas I. Jensen |
| author_facet | Natan J. W. Straathof Charlotte B. Magnus Fedor Zhuravlev Andreas I. Jensen |
| author_sort | Natan J. W. Straathof |
| collection | DOAJ |
| description | The field of targeted radionuclide therapy is rapidly growing, highlighting the need for wider radionuclide availability. Soft Lewis acid ions, such as radioisotopes of platinum, rhodium and palladium, are particularly underdeveloped. This is due in part to a lack of compatible bifunctional chelators. These allow for the practical bioconjugation to targeting vectors, in turn enabling radiolabeling. The [16]andS<sub>4</sub> macrocycle has been reported to chelate a number of relevant soft metal ions. In this work, we present a procedure for synthesizing [16]andS<sub>4</sub> in 45% yield (five steps, 12% overall yield), together with a selection of strategies for preparing bifunctional derivatives. An ester-linked N-hydroxysuccimide ester (NHS, seven steps, 4% overall yield), an ether-linked isothiocyanate (NCS, eight steps, 5% overall yield) and an azide derivative were prepared. In addition, a new route to a carbon-carbon linked carboxylic acid functionalized derivative is presented. Finally, a general method for conjugating the NHS and NCS derivatives to a polar peptide (octreotide) is presented, by dissolution in water:acetonitrile (1:1), buffered to pH 9.4 using borate. The reported compounds will be readily applicable in radiopharmaceutical chemistry, by facilitating the labeling of a range of molecules, including peptides, with relevant soft radiometal ions. |
| first_indexed | 2024-03-10T09:10:50Z |
| format | Article |
| id | doaj.art-1e3873fe98f94e7c8fd1e43c587d9191 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T09:10:50Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-1e3873fe98f94e7c8fd1e43c587d91912023-11-22T06:00:30ZengMDPI AGMolecules1420-30492021-07-012615460310.3390/molecules26154603Novel Bifunctional [16]aneS<sub>4</sub>-Derived Chelators for Soft RadiometalsNatan J. W. Straathof0Charlotte B. Magnus1Fedor Zhuravlev2Andreas I. Jensen3Department of Health Technology (DTU Health Tech), Technical University of Denmark (DTU), Frederiksborgvej 399, 4000 Roskilde, DenmarkDepartment of Health Technology (DTU Health Tech), Technical University of Denmark (DTU), Frederiksborgvej 399, 4000 Roskilde, DenmarkDepartment of Health Technology (DTU Health Tech), Technical University of Denmark (DTU), Frederiksborgvej 399, 4000 Roskilde, DenmarkDepartment of Health Technology (DTU Health Tech), Technical University of Denmark (DTU), Frederiksborgvej 399, 4000 Roskilde, DenmarkThe field of targeted radionuclide therapy is rapidly growing, highlighting the need for wider radionuclide availability. Soft Lewis acid ions, such as radioisotopes of platinum, rhodium and palladium, are particularly underdeveloped. This is due in part to a lack of compatible bifunctional chelators. These allow for the practical bioconjugation to targeting vectors, in turn enabling radiolabeling. The [16]andS<sub>4</sub> macrocycle has been reported to chelate a number of relevant soft metal ions. In this work, we present a procedure for synthesizing [16]andS<sub>4</sub> in 45% yield (five steps, 12% overall yield), together with a selection of strategies for preparing bifunctional derivatives. An ester-linked N-hydroxysuccimide ester (NHS, seven steps, 4% overall yield), an ether-linked isothiocyanate (NCS, eight steps, 5% overall yield) and an azide derivative were prepared. In addition, a new route to a carbon-carbon linked carboxylic acid functionalized derivative is presented. Finally, a general method for conjugating the NHS and NCS derivatives to a polar peptide (octreotide) is presented, by dissolution in water:acetonitrile (1:1), buffered to pH 9.4 using borate. The reported compounds will be readily applicable in radiopharmaceutical chemistry, by facilitating the labeling of a range of molecules, including peptides, with relevant soft radiometal ions.https://www.mdpi.com/1420-3049/26/15/4603sulfur containing macrocyclesbifunctional chelatorsbio-conjugationradiation therapy |
| spellingShingle | Natan J. W. Straathof Charlotte B. Magnus Fedor Zhuravlev Andreas I. Jensen Novel Bifunctional [16]aneS<sub>4</sub>-Derived Chelators for Soft Radiometals Molecules sulfur containing macrocycles bifunctional chelators bio-conjugation radiation therapy |
| title | Novel Bifunctional [16]aneS<sub>4</sub>-Derived Chelators for Soft Radiometals |
| title_full | Novel Bifunctional [16]aneS<sub>4</sub>-Derived Chelators for Soft Radiometals |
| title_fullStr | Novel Bifunctional [16]aneS<sub>4</sub>-Derived Chelators for Soft Radiometals |
| title_full_unstemmed | Novel Bifunctional [16]aneS<sub>4</sub>-Derived Chelators for Soft Radiometals |
| title_short | Novel Bifunctional [16]aneS<sub>4</sub>-Derived Chelators for Soft Radiometals |
| title_sort | novel bifunctional 16 anes sub 4 sub derived chelators for soft radiometals |
| topic | sulfur containing macrocycles bifunctional chelators bio-conjugation radiation therapy |
| url | https://www.mdpi.com/1420-3049/26/15/4603 |
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