Novel and efficient method for solid phase synthesis of urea-containing peptides targeting prostate specific membrane antigen (PSMA) in comparison with current methods

نویسندگان

  • Davood Beiki Research Institute for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Farzad Kobarfard Department of Pharmaceutical Chemistry and Radiopharmacy, School of Pharmacy, Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences
  • Khosrou Abdi Department of Radiopharmacy and Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  • Mohsen Amini Associate professor of Medicinal Chemistry Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  • Mona Mosayebnia Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences,Tehran.Iran.
  • Omid Sabzevari Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • Pedram Rikhtechi Department of Pharmaceutical Chemistry and Radiopharmacy, School of Pharmacy, Shahid Behesti University of Medical Sciences,Tehran,Iran.
  • Sedigheh Rezaeianpour Department of Pharmaceutical Chemistry and Radiopharmacy, School of Pharmacy, Shahid Behesti University of Medical Sciences,Tehran,Iran.
  • Soraya Shahhosseini Department of Pharmaceutical Chemistry and Radiopharmacy, School of Pharmacy, Shahid Behesti University of Medical Sciences, Tehran, Iran.|Protein Technology Research Center, Shahid Behesti University of Medical Sciences, Tehran, Iran.
  • Zahra Hajimahdi Department of Pharmaceutical Chemistry and Radiopharmacy, School of Pharmacy, Shahid Behesti University of Medical Sciences,tehran,Iran.
چکیده مقاله:

The basic chemical structure of most prostate specific membrane antigen (PSMA) inhibitors which are now in pre-clinical and clinical studies is Glu-Ureido-based peptides. Synthesis of urea-based PSMA inhibitors includes two steps: 1- isocyanate intermediate formation and 2- urea bond formation. In current methods, isocyanate is formed in liquid phase and then reacts with amine existing in liquid phase or bound to solid phase for urea bond formation. In this study, we developed a new facile method for formation of both isocyanate and urea on solid phase under standard peptide coupling conditions. The solid phase-bound isocyanate served as intermediate to form urea bond. To monitor reaction progress qualitative test (Kaiser Test) and On-Bead FT-IR spectroscopy were used. The structure of Glutamate-Urea-Lysine (EUK) was confirmed using LC-Mass and 1H-NMR. This novel method successfully applied to synthesize of another urea-based peptide containing a sequence of Glu-Urea-Lys(OMe)-GABA-Tyr-Tyr-GABA and the bifunctional linker hydrazinonicotinamide (HYNIC) as well.

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عنوان ژورنال

دوره 17  شماره 3

صفحات  917- 926

تاریخ انتشار 2018-07-01

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