Polypeptide-Based Molecular Platform and Its Docetaxel/Sulfo-Cy5-Containing Conjugate for Targeted Delivery to Prostate Specific Membrane Antigen

Stanislav A. Petrov; Aleksei E. Machulkin; Anastasia A. Uspenskaya; Nikolay Y. Zyk; Ekaterina A. Nimenko; Anastasia S. Garanina; Rostislav A. Petrov; Vladimir I. Polshakov; Yuri K. Grishin; Vitaly A. Roznyatovsky; Nikolay V. Zyk; Alexander G. Majouga; Elena K. Beloglazkina

doi:10.3390/molecules25245784

Molecules (Dec 2020)

Polypeptide-Based Molecular Platform and Its Docetaxel/Sulfo-Cy5-Containing Conjugate for Targeted Delivery to Prostate Specific Membrane Antigen

Stanislav A. Petrov,
Aleksei E. Machulkin,
Anastasia A. Uspenskaya,
Nikolay Y. Zyk,
Ekaterina A. Nimenko,
Anastasia S. Garanina,
Rostislav A. Petrov,
Vladimir I. Polshakov,
Yuri K. Grishin,
Vitaly A. Roznyatovsky,
Nikolay V. Zyk,
Alexander G. Majouga,
Elena K. Beloglazkina

Affiliations

Stanislav A. Petrov: Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia
Aleksei E. Machulkin: Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia
Anastasia A. Uspenskaya: Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia
Nikolay Y. Zyk: Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia
Ekaterina A. Nimenko: Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia
Anastasia S. Garanina: Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia
Rostislav A. Petrov: Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia
Vladimir I. Polshakov: Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky Ave., 27-1, 119991 Moscow, Russia
Yuri K. Grishin: Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia
Vitaly A. Roznyatovsky: Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia
Nikolay V. Zyk: Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia
Alexander G. Majouga: Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia
Elena K. Beloglazkina: Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia

DOI: https://doi.org/10.3390/molecules25245784
Journal volume & issue: Vol. 25, no. 24
p. 5784

Abstract

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A strategy for stereoselective synthesis of molecular platform for targeted delivery of bimodal therapeutic or theranostic agents to the prostate-specific membrane antigen (PSMA) receptor was developed. The proposed platform contains a urea-based, PSMA-targeting Glu-Urea-Lys (EuK) fragment as a vector moiety and tripeptide linker with terminal amide and azide groups for subsequent addition of two different therapeutic and diagnostic agents. The optimal method for this molecular platform synthesis includes (a) solid-phase assembly of the polypeptide linker, (b) coupling of this linker with the vector fragment, (c) attachment of 3-aminopropylazide, and (d) amide and carboxylic groups deprotection. A bimodal theranostic conjugate of the proposed platform with a cytostatic drug (docetaxel) and a fluorescent label (Sulfo-Cy5) was synthesized to demonstrate its possible sequential conjugation with different functional molecules.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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