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

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 24; p. 5784
• Main Authors: Petrov, Stanislav A., Machulkin, Aleksei E., Uspenskaya, Anastasia A., Zyk, Nikolay Y., Nimenko, Ekaterina A., Garanina, Anastasia S., Petrov, Rostislav A., Polshakov, Vladimir I., Grishin, Yuri K., Roznyatovsky, Vitaly A., Zyk, Nikolay V., Majouga, Alexander G., Beloglazkina, Elena K.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.12.2020; MDPI
• Subjects: Amino Acid Sequence; Amino acids; anticancer drugs; Antigens; Antigens, Surface - administration & dosage; Binding sites; Cancer therapies; Carbocyanines - chemistry; Chemistry Techniques, Synthetic; docetaxel; Docetaxel - chemistry; Drug Carriers - chemistry; Drug Delivery Systems; Glutamate Carboxypeptidase II - administration & dosage; Ligands; Medical diagnosis; Molecular Structure; peptide synthesis; Peptides - chemical synthesis; Peptides - chemistry; Polymers; Polypeptides; Prostate cancer; PSMA conjugate; theranostic agent; prostate cancer; docetaxel; theranostic agent; anticancer drugs; PSMA conjugate; peptide synthesis; Sulfo-Cy5
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25245784

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.