Design and synthesis of a bis(cycloisodityrosine) analogue of RA-VII, an antitumor bicyclic hexapeptide.
An analogue of an antitumor bicyclic hexapeptide RA-VII was prepared, in which the Ala-2 and Tyr-3 residues of RA-VII were replaced by a cycloisodityrosine unit. In the crystalline state, the peptide backbone structures and the side-chain conformations at Tyr-3, Tyr-5, and Tyr-6 of this analogue and of RA-II were very similar. This analogue, however, showed much weaker cytotoxicity against P-388 leukemia cells than parent RA-VII.
Lee
Ji-Ean
JE
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Hitotsuyanagi
Yukio
Y
Nakagawa
Yoshie
Y
Kato
Saori
S
Fukaya
Haruhiko
H
Takeya
Koichi
K
D002626:Chemistry, Pharmaceutical / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000378:metabolism; D045470:Rubia / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry
D010455:Peptides; D010456:Peptides, Cyclic; D010936:Plant Extracts; C018234:bouvardin; D014443:Tyrosine; C043548:RA VII