10 results on '"Motz, Rachel N."'
Search Results
2. "Off‐Label Use" of the Siderophore Enterobactin Enables Targeted Imaging of Cancer with Radioactive Ti(IV).
- Author
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Koller, Angus J., Glaser, Owen, DeLuca, Molly C., Motz, Rachel N., Amason, Edith K., Carbo‐Bague, Imma, Mixdorf, Jason C., Guzei, Ilia A., Aluicio‐Sarduy, Eduardo, Śmiłowicz, Dariusz, Barnhart, Todd E., Ramogida, Caterina F., Nolan, Elizabeth M., Engle, Jonathan W., and Boros, Eszter
- Subjects
OFF-label use (Drugs) ,BLOOD proteins ,SMALL molecules ,NUCLEAR medicine ,RADIOISOTOPES ,RADIOLABELING - Abstract
The development of inert, biocompatible chelation methods is required to harness the emerging positron emitting radionuclide 45Ti for radiopharmaceutical applications. Herein, we evaluate the Ti(IV)‐coordination chemistry of four catechol‐based, hexacoordinate chelators using synthetic, structural, computational, and radiochemical approaches. The siderophore enterobactin (Ent) and its synthetic mimic TREN‐CAM readily form mononuclear Ti(IV) species in aqueous solution at neutral pH. Radiolabeling studies reveal that Ent and TREN‐CAM form mononuclear complexes with the short‐lived, positron‐emitting radionuclide 45Ti(IV), and do not transchelate to plasma proteins in vitro and exhibit rapid renal clearance in naïve mice. These features guide efforts to target the 45Ti isotope to prostate cancer tissue through the design, synthesis, and evaluation of Ent‐DUPA, a small molecule conjugate composed of a prostate specific membrane antigen (PSMA) targeting peptide and a monofunctionalized Ent scaffold. The [45Ti][Ti(Ent‐DUPA)]2− complex forms readily at room temperature. In a tumor xenograft model in mice, selective tumor tissue accumulation (8±5 %, n=5), and low off‐target uptake in other organs is observed. Overall, this work demonstrates targeted imaging with 45Ti(IV), provides a foundation for advancing the application of 45Ti in nuclear medicine, and reveals that Ent can be repurposed as a 45Ti‐complexing cargo for targeted nuclear imaging applications. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. "Off‐Label Use" of the Siderophore Enterobactin Enables Targeted Imaging of Cancer with Radioactive Ti(IV).
- Author
-
Koller, Angus J., Glaser, Owen, DeLuca, Molly C., Motz, Rachel N., Amason, Edith K., Carbo‐Bague, Imma, Mixdorf, Jason C., Guzei, Ilia A., Aluicio‐Sarduy, Eduardo, Śmiłowicz, Dariusz, Barnhart, Todd E., Ramogida, Caterina F., Nolan, Elizabeth M., Engle, Jonathan W., and Boros, Eszter
- Subjects
OFF-label use (Drugs) ,BLOOD proteins ,SMALL molecules ,NUCLEAR medicine ,RADIOISOTOPES ,RADIOLABELING - Abstract
The development of inert, biocompatible chelation methods is required to harness the emerging positron emitting radionuclide 45Ti for radiopharmaceutical applications. Herein, we evaluate the Ti(IV)‐coordination chemistry of four catechol‐based, hexacoordinate chelators using synthetic, structural, computational, and radiochemical approaches. The siderophore enterobactin (Ent) and its synthetic mimic TREN‐CAM readily form mononuclear Ti(IV) species in aqueous solution at neutral pH. Radiolabeling studies reveal that Ent and TREN‐CAM form mononuclear complexes with the short‐lived, positron‐emitting radionuclide 45Ti(IV), and do not transchelate to plasma proteins in vitro and exhibit rapid renal clearance in naïve mice. These features guide efforts to target the 45Ti isotope to prostate cancer tissue through the design, synthesis, and evaluation of Ent‐DUPA, a small molecule conjugate composed of a prostate specific membrane antigen (PSMA) targeting peptide and a monofunctionalized Ent scaffold. The [45Ti][Ti(Ent‐DUPA)]2− complex forms readily at room temperature. In a tumor xenograft model in mice, selective tumor tissue accumulation (8±5 %, n=5), and low off‐target uptake in other organs is observed. Overall, this work demonstrates targeted imaging with 45Ti(IV), provides a foundation for advancing the application of 45Ti in nuclear medicine, and reveals that Ent can be repurposed as a 45Ti‐complexing cargo for targeted nuclear imaging applications. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Conjugation to Native and Nonnative Triscatecholate Siderophores Enhances Delivery and Antibacterial Activity of a β‑Lactam to Gram-Negative Bacterial Pathogens.
- Author
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Motz, Rachel N., Guo, Chuchu, Sargun, Artur, Walker, Gregory T., Sassone-Corsi, Martina, Raffatellu, Manuela, and Nolan, Elizabeth M.
- Published
- 2024
- Full Text
- View/download PDF
5. High-Throughput Screening of Earth-Abundant Water Reduction Catalysts toward Photocatalytic Hydrogen Evolution
- Author
-
Motz, Rachel N., primary, Lopato, Eric M., additional, Connell, Timothy U., additional, and Bernhard, Stefan, additional
- Published
- 2021
- Full Text
- View/download PDF
6. "Off‐Label Use" of the Siderophore Enterobactin Enables Targeted Imaging of Cancer with Radioactive Ti(IV).
- Author
-
Koller, Angus J., Glaser, Owen, DeLuca, Molly C., Motz, Rachel N., Amason, Edith K., Carbo‐Bague, Imma, Mixdorf, Jason C., Guzei, Ilia A., Aluicio‐Sarduy, Eduardo, Śmiłowicz, Dariusz, Barnhart, Todd E., Ramogida, Caterina F., Nolan, Elizabeth M., Engle, Jonathan W., and Boros, Eszter
- Subjects
- *
OFF-label use (Drugs) , *BLOOD proteins , *SMALL molecules , *NUCLEAR medicine , *RADIOISOTOPES , *RADIOLABELING - Abstract
The development of inert, biocompatible chelation methods is required to harness the emerging positron emitting radionuclide 45Ti for radiopharmaceutical applications. Herein, we evaluate the Ti(IV)‐coordination chemistry of four catechol‐based, hexacoordinate chelators using synthetic, structural, computational, and radiochemical approaches. The siderophore enterobactin (Ent) and its synthetic mimic TREN‐CAM readily form mononuclear Ti(IV) species in aqueous solution at neutral pH. Radiolabeling studies reveal that Ent and TREN‐CAM form mononuclear complexes with the short‐lived, positron‐emitting radionuclide 45Ti(IV), and do not transchelate to plasma proteins in vitro and exhibit rapid renal clearance in naïve mice. These features guide efforts to target the 45Ti isotope to prostate cancer tissue through the design, synthesis, and evaluation of Ent‐DUPA, a small molecule conjugate composed of a prostate specific membrane antigen (PSMA) targeting peptide and a monofunctionalized Ent scaffold. The [45Ti][Ti(Ent‐DUPA)]2− complex forms readily at room temperature. In a tumor xenograft model in mice, selective tumor tissue accumulation (8±5 %, n=5), and low off‐target uptake in other organs is observed. Overall, this work demonstrates targeted imaging with 45Ti(IV), provides a foundation for advancing the application of 45Ti in nuclear medicine, and reveals that Ent can be repurposed as a 45Ti‐complexing cargo for targeted nuclear imaging applications. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
7. "Off‐Label Use" of the Siderophore Enterobactin Enables Targeted Imaging of Cancer with Radioactive Ti(IV).
- Author
-
Koller, Angus J., Glaser, Owen, DeLuca, Molly C., Motz, Rachel N., Amason, Edith K., Carbo‐Bague, Imma, Mixdorf, Jason C., Guzei, Ilia A., Aluicio‐Sarduy, Eduardo, Śmiłowicz, Dariusz, Barnhart, Todd E., Ramogida, Caterina F., Nolan, Elizabeth M., Engle, Jonathan W., and Boros, Eszter
- Subjects
- *
OFF-label use (Drugs) , *BLOOD proteins , *SMALL molecules , *NUCLEAR medicine , *RADIOISOTOPES , *RADIOLABELING - Abstract
The development of inert, biocompatible chelation methods is required to harness the emerging positron emitting radionuclide 45Ti for radiopharmaceutical applications. Herein, we evaluate the Ti(IV)‐coordination chemistry of four catechol‐based, hexacoordinate chelators using synthetic, structural, computational, and radiochemical approaches. The siderophore enterobactin (Ent) and its synthetic mimic TREN‐CAM readily form mononuclear Ti(IV) species in aqueous solution at neutral pH. Radiolabeling studies reveal that Ent and TREN‐CAM form mononuclear complexes with the short‐lived, positron‐emitting radionuclide 45Ti(IV), and do not transchelate to plasma proteins in vitro and exhibit rapid renal clearance in naïve mice. These features guide efforts to target the 45Ti isotope to prostate cancer tissue through the design, synthesis, and evaluation of Ent‐DUPA, a small molecule conjugate composed of a prostate specific membrane antigen (PSMA) targeting peptide and a monofunctionalized Ent scaffold. The [45Ti][Ti(Ent‐DUPA)]2− complex forms readily at room temperature. In a tumor xenograft model in mice, selective tumor tissue accumulation (8±5 %, n=5), and low off‐target uptake in other organs is observed. Overall, this work demonstrates targeted imaging with 45Ti(IV), provides a foundation for advancing the application of 45Ti in nuclear medicine, and reveals that Ent can be repurposed as a 45Ti‐complexing cargo for targeted nuclear imaging applications. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
8. "Off-Label Use" of the Siderophore Enterobactin Enables Targeted Imaging of Cancer with Radioactive Ti (IV) .
- Author
-
Koller AJ, Glaser O, DeLuca MC, Motz RN, Amason EK, Carbo-Bague I, Mixdorf JC, Guzei IA, Aluicio-Sarduy E, Śmiłowicz D, Barnhart TE, Ramogida CF, Nolan EM, Engle JW, and Boros E
- Subjects
- Humans, Male, Animals, Mice, Enterobactin metabolism, Titanium chemistry, Off-Label Use, Radioisotopes, Siderophores chemistry, Prostatic Neoplasms metabolism
- Abstract
The development of inert, biocompatible chelation methods is required to harness the emerging positron emitting radionuclide
45 Ti for radiopharmaceutical applications. Herein, we evaluate the Ti(IV) -coordination chemistry of four catechol-based, hexacoordinate chelators using synthetic, structural, computational, and radiochemical approaches. The siderophore enterobactin (Ent) and its synthetic mimic TREN-CAM readily form mononuclear Ti(IV) species in aqueous solution at neutral pH. Radiolabeling studies reveal that Ent and TREN-CAM form mononuclear complexes with the short-lived, positron-emitting radionuclide45 Ti(IV) , and do not transchelate to plasma proteins in vitro and exhibit rapid renal clearance in naïve mice. These features guide efforts to target the45 Ti isotope to prostate cancer tissue through the design, synthesis, and evaluation of Ent-DUPA, a small molecule conjugate composed of a prostate specific membrane antigen (PSMA) targeting peptide and a monofunctionalized Ent scaffold. The [45 Ti][Ti(Ent-DUPA)]2- complex forms readily at room temperature. In a tumor xenograft model in mice, selective tumor tissue accumulation (8±5 %, n=5), and low off-target uptake in other organs is observed. Overall, this work demonstrates targeted imaging with45 Ti(IV) , provides a foundation for advancing the application of45 Ti in nuclear medicine, and reveals that Ent can be repurposed as a45 Ti-complexing cargo for targeted nuclear imaging applications., (© 2024 Wiley‐VCH GmbH.)- Published
- 2024
- Full Text
- View/download PDF
9. Experimental methods for evaluating siderophore-antibiotic conjugates.
- Author
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Motz RN, Kamyabi G, and Nolan EM
- Subjects
- Microbial Sensitivity Tests methods, Siderophores chemistry, Siderophores pharmacology, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Enterobactin chemistry, Enterobactin metabolism
- Abstract
Siderophore-antibiotic conjugates (SACs) are of past and current interest for delivering antibacterials into Gram-negative bacterial pathogens that express siderophore receptors. Studies of SACs are often multifaceted and involve chemical and biological approaches. Major goals are to evaluate the antimicrobial activity and uptake of novel SACs and use the resulting data to inform further mode-of-action studies and molecular design strategies. In this chapter, we describe four key methods that we apply when investigating the antimicrobial activity and uptake of novel SACs based on the siderophore enterobactin (Ent). These methods are based on approaches from the siderophore literature as well as established protocols for antimicrobial activity testing, and include assays for evaluating SAC antimicrobial activity, time-kill kinetics, siderophore competition, and bacterial cell uptake using
57 Fe. These assays have served us well in characterizing our Ent-based conjugates and can be applied to study SACs that use other siderophores as targeting vectors., (Copyright © 2024. Published by Elsevier Inc.)- Published
- 2024
- Full Text
- View/download PDF
10. High-Throughput Determination of Stern-Volmer Quenching Constants for Common Photocatalysts and Quenchers.
- Author
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Motz RN, Sun AC, Lehnherr D, and Ruccolo S
- Abstract
Mechanistic information on reactions proceeding via photoredox catalysis has enabled rational optimizations of existing reactions and revealed new synthetic pathways. One essential step in any photoredox reaction is catalyst quenching via photoinduced electron transfer or energy transfer with either a substrate, additive, or cocatalyst. Identification of the correct quencher using Stern-Volmer studies is a necessary step for mechanistic understanding; however, such studies are often cumbersome, low throughput and require specialized luminescence instruments. This report describes a high-throughput method to rapidly acquire a series of Stern-Volmer constants, employing readily available fluorescence plate readers and 96-well plates. By leveraging multichannel pipettors or liquid dispensing robots in combination with fast plate readers, the sampling frequency for quenching studies can be improved by several orders of magnitude. This new high-throughput method enabled the rapid collection of 220 quenching constants for a library of 20 common photocatalysts with 11 common quenchers. The extensive Stern-Volmer constant table generated greatly facilitates the systematic comparison between quenchers and can provide guidance to the synthetic community interested in designing and understanding catalytic photoredox reactions., Competing Interests: The authors declare no competing financial interest., (© 2023 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. Published by American Chemical Society.)
- Published
- 2023
- Full Text
- View/download PDF
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