Synthesis of Bispidine-Based Prostate-Specific Membrane Antigen-Targeted Conjugate and Initial Investigations

Synthesis of Bispidine-Based Prostate-Specific Membrane Antigen-Targeted Conjugate and Initial Investigations Full article

Journal

Organics
ISSN: 2673-401X

Output data

Year: 2025, Volume: 6, Number: 1, Article number : 7, Pages count : DOI: 10.3390/org6010007

Authors

Machulkin Aleksei E. ^1,2 , Petrov Stanislav A. ¹ , Kraynova Maria D. ¹ , Garanina Anastasiia S. ³ , Egorova Bayirta V. ¹ , Timoshenko Roman V. ⁴ , Vaneev Alexander N. ^1,4 , Erofeev Alexander S. ^1,4 , Priselkova Anna B. ⁵ , Kalinin Mikhail A. ¹ , Medved′ko Aleksei V. ⁶ , Kalmykov Stepan N. ^1,7 , Beloglazkina Elena K. ¹ , Vatsadze Sergey Z. ⁶

Affiliations

1	Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, Moscow 119991, Russia
2	Department for Biochemistry, People’s Friendship University of Russia Named after Patrice Lumumba, Moscow 117198, Russia
3	Laboratory of Biomedical Nanomaterials, National University of Science and Technology MISiS, 4 Leninskiy pr, Moscow 119049, Russia
4	Laboratory of Biophysics, National University of Science and Technology MISiS, 4 Leninskiy pr, Moscow 119049, Russia
5	Nuclear Reactions Division, Skobeltsyn Institute of Nuclear Physics, Lomonosov Moscow State University, Leninskie Gory, Building 1/2, GSP-1, Moscow 119991, Russia
6	Laboratory of Supramolecular Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia
7	Frumkin Institute of Physical Chemistry and Electrochemistry Russian Academy of Sciences (IPCE RAS), Moscow 119071, Russia

Nowadays, PSMA ligands are widely used for radiotheragnostic purposes in prostate cancer. The synthesis of a PSMA-Bisp conjugate was developed and realized with good yield (overall yield ~58% for the last two steps). All newly synthesized compounds were characterized by physicochemical methods: 1H and 13C NMR, HRMS, and LCMS (for biologically tested samples). Subsequently, Bisp1 (diacetate bispidine ligand), Bisp-alkyne (bifunctional derivative of Bisp1), and its conjugate PSMA-Bisp were labeled by 64Cu in mild conditions. In vitro studies of the labeled conjugate [64Cu]Cu-PSMA-Bisp have shown great stability in model solutions. Finally, [64Cu]Cu-PSMA-Bisp was compared to the well-known PSMA-617 conjugate labeled with 64Cu and they showed similar stability in excess bovine serum (BVS), and at the same time, labeling PSMA-Bisp with 64Cu is characterized by extremely high kinetics in mild conditions, while labeling PSMA-617 with 64Cu requires heating (90 °C). Thus, this conjugate can be incredibly promising for nuclear medicine.

Machulkin A.E. , Petrov S.A. , Kraynova M.D. , Garanina A.S. , Egorova B.V. , Timoshenko R.V. , Vaneev A.N. , Erofeev A.S. , Priselkova A.B. , Kalinin M.A. , Medved′ko A.V. , Kalmykov S.N. , Beloglazkina E.K. , Vatsadze S.Z.
Synthesis of Bispidine-Based Prostate-Specific Membrane Antigen-Targeted Conjugate and Initial Investigations
Organics. 2025. V.6. N1. 7 . DOI: 10.3390/org6010007 OpenAlex

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