2. Academic Validation
  3. Synthesis of [Tyr-5-Ψ(CH2NMe)-Tyr-6]RA-VII, a reduced peptide bond analogue of RA-VII, an antitumor bicyclic hexapeptide

Synthesis of [Tyr-5-Ψ(CH2NMe)-Tyr-6]RA-VII, a reduced peptide bond analogue of RA-VII, an antitumor bicyclic hexapeptide

  • Bioorg Med Chem Lett. 2012 Apr 15;22(8):2757-9. doi: 10.1016/j.bmcl.2012.02.093.
Tomoyo Hasuda 1,  Yukio Hitotsuyanagi,  Mitsuyuki Shinada,  Koichi Takeya
Affiliations

Affiliation

  • 1 School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
PMID: 22460024 DOI: 10.1016/j.bmcl.2012.02.093
Abstract

A reduced peptide bond analogue of RA-VII, [Tyr-5-Ψ(CH(2)NMe)-Tyr-6]RA-VII (3), was designed and synthesized. The key reduced cycloisodityrosine unit was prepared by reduction of the cycloisodityrosine derived from natural RA-VII, followed by connection with the tetrapeptide segment to afford a hexapeptide. Subsequent macrocyclization of the hexapeptide with FDPP under dilute conditions gave 3. Analogue 3 showed cytotoxic activity against P-388 cells, but its activity was much weaker than that of parent peptide RA-VII.

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