Synthesis and Biological Evaluation of PSMA Ligands with Aromatic Residues and Fluorescent Conjugates Based on Them
- Aleksei E. Machulkin*Aleksei E. Machulkin*Email: [email protected]Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationMore by Aleksei E. Machulkin
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- Radik R. ShafikovRadik R. ShafikovChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationShemyakin and Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, GSP-7, Ulitsa Miklukho-Maklaya, 16/10, Moscow 117997, Russian FederationMore by Radik R. Shafikov
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- Anastasia A. UspenskayaAnastasia A. UspenskayaChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationMore by Anastasia A. Uspenskaya
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- Stanislav A. PetrovStanislav A. PetrovChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationMore by Stanislav A. Petrov
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- Anton P. BerAnton P. BerChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationMore by Anton P. Ber
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- Dmitry A. SkvortsovDmitry A. SkvortsovChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationFaculty of Biology and Biotechnologies, Higher School of Economics, Myasnitskaya 13, Moscow 101000, RussiaMore by Dmitry A. Skvortsov
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- Ekaterina A. NimenkoEkaterina A. NimenkoChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationMore by Ekaterina A. Nimenko
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- Nikolay U. ZykNikolay U. ZykChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationMore by Nikolay U. Zyk
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- Galina B. SmirnovaGalina B. SmirnovaN.N. Blokhin Cancer Research Center, 24 Kashirskoye sh., Moscow 115478 , RussiaMore by Galina B. Smirnova
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- Vadim S. PokrovskyVadim S. PokrovskyN.N. Blokhin Cancer Research Center, 24 Kashirskoye sh., Moscow 115478 , RussiaRUDN University, Miklukho-Maklaya str. 6, Moscow 117198, Russian FederationMore by Vadim S. Pokrovsky
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- Maxim A. AbakumovMaxim A. AbakumovNational University of Science and Technology MISiS, 9 Leninskiy pr., Moscow 119049, Russian FederationMore by Maxim A. Abakumov
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- Irina V. SaltykovaIrina V. SaltykovaChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationMore by Irina V. Saltykova
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- Rauf T. AkhmirovRauf T. AkhmirovDmitry Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, Moscow 125047, Russian FederationMore by Rauf T. Akhmirov
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- Anastasiia S. GaraninaAnastasiia S. GaraninaNational University of Science and Technology MISiS, 9 Leninskiy pr., Moscow 119049, Russian FederationMore by Anastasiia S. Garanina
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- Vladimir I. PolshakovVladimir I. PolshakovCenter for Magnetic Tomography and Spectroscopy, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow 119991, Russian FederationMore by Vladimir I. Polshakov
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- Oleg Y. SavelievOleg Y. SavelievCenter for Magnetic Tomography and Spectroscopy, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow 119991, Russian FederationMore by Oleg Y. Saveliev
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- Yan A. IvanenkovYan A. IvanenkovChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationMoscow Institute of Physics and Technology (State University), 9 Institutskiy Lane, Dolgoprudny City, Moscow Region 141700, Russian FederationNational University of Science and Technology MISiS, 9 Leninskiy pr., Moscow 119049, Russian FederationThe Federal State Unitary Enterprise Dukhov Automatics Research Institute, Moscow 127055, RussiaInstitute of Biochemistry and Genetics Ufa Science Centre Russian Academy of Sciences (IBG RAS), Oktyabrya Prospekt 71, Ufa 450054, Russian FederationMore by Yan A. Ivanenkov
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- Anastasiya V. AladinskayaAnastasiya V. AladinskayaMoscow Institute of Physics and Technology (State University), 9 Institutskiy Lane, Dolgoprudny City, Moscow Region 141700, Russian FederationMore by Anastasiya V. Aladinskaya
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- Alexander V. FinkoAlexander V. FinkoChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationMore by Alexander V. Finko
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- Emil U. YamansarovEmil U. YamansarovChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationMore by Emil U. Yamansarov
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- Olga O. KrasnovskayaOlga O. KrasnovskayaChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationNational University of Science and Technology MISiS, 9 Leninskiy pr., Moscow 119049, Russian FederationMore by Olga O. Krasnovskaya
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- Alexander S. ErofeevAlexander S. ErofeevChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationNational University of Science and Technology MISiS, 9 Leninskiy pr., Moscow 119049, Russian FederationMore by Alexander S. Erofeev
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- Petr V. GorelkinPetr V. GorelkinChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationNational University of Science and Technology MISiS, 9 Leninskiy pr., Moscow 119049, Russian FederationMore by Petr V. Gorelkin
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- Olga A. DontsovaOlga A. DontsovaChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationShemyakin and Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, GSP-7, Ulitsa Miklukho-Maklaya, 16/10, Moscow 117997, Russian FederationMore by Olga A. Dontsova
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- Elena K. BeloglazkinaElena K. BeloglazkinaChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationMore by Elena K. Beloglazkina
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- Nikolay V. ZykNikolay V. ZykChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationMore by Nikolay V. Zyk
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- Elena S. KhazanovaElena S. KhazanovaIzvarino Pharma LLC, v. Vnukovskoe, Vnukovskoe sh., 5th km., Building 1, Moscow 108817, Russian FederationMore by Elena S. Khazanova
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- Alexander G. MajougaAlexander G. MajougaChemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russian FederationNational University of Science and Technology MISiS, 9 Leninskiy pr., Moscow 119049, Russian FederationDmitry Mendeleev University of Chemical Technology of Russia, Miusskaya sq. 9, Moscow 125047, Russian FederationMore by Alexander G. Majouga
Abstract
Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), is a suitable target for specific delivery of antitumor drugs and diagnostic agents due to its overexpression in prostate cancer cells. In the current work, we describe the design, synthesis, and biological evaluation of novel low-molecular PSMA ligands and conjugates with fluorescent dyes FAM-5, SulfoCy5, and SulfoCy7. In vitro evaluation of synthesized PSMA ligands on the activity of PSMA shows that the addition of aromatic amino acids into a linker structure leads to a significant increase in inhibition. The conjugates of the most potent ligand with FAM-5 as well as SulfoCy5 demonstrated high affinities to PSMA-expressing tumor cells in vitro. In vivo biodistribution in 22Rv1 xenografts in Balb/c nude mice of PSMA-SulfoCy5 and PSMA-SulfoCy7 conjugates with a novel PSMA ligand demonstrated good visualization of PSMA-expressing tumors. Also, the conjugate PSMA-SulfoCy7 demonstrated the absence of any explicit toxicity up to 87.9 mg/kg.
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