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

Molecules

NikolayV. Zyk¹  NikolayY. Zyk¹  YuriK. Grishin¹  VitalyA. Roznyatovsky¹  AnastasiaS. Garanina¹  RostislavA. Petrov¹  EkaterinaA. Nimenko¹  AlekseiE. Machulkin¹  AlexanderG. Majouga¹  StanislavA. Petrov¹  ElenaK. Beloglazkina¹  AnastasiaA. Uspenskaya¹  VladimirI. Polshakov² 

[1] Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia;Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky Ave., 27-1, 119991 Moscow, Russia;

关键词: theranostic agent;    peptide synthesis;    prostate cancer;    anticancer drugs;    PSMA conjugate;    docetaxel;   

DOI  :  10.3390/molecules25245784

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown