title: Conformational transformation of ascidiacyclamide analogues induced by incorporating enantiomers of phenylalanine, 1-naphthylalanine or 2-naphthylalanine.
abstract: We designed five ascidiacyclamide analogues [cyclo(-Xxx(1) -oxazoline(2) -d-Val(3) -thiazole(4) -l-Ile(5) -oxazoline(6) -d-Val(7) -thiazole(8) -)] incorporating l-1-naphthylalanine (l-1Nal), l-2-naphthylalanine (l-2Nal), d-phenylalanine (d-Phe), d-1-naphthylalanine (d-1Nal) or d-2-naphthylalanine (d-2Nal) into the Xxx(1) position of the peptide. The conformations of these analogues were then examined using (1) H NMR, CD spectroscopy, and X-ray diffraction. These analyses suggested that d-enantiomer-incorporated ASCs [(d-Phe), (d-1Nal), and (d-2Nal)ASC] transformed from the folded to the open structure in solution more easily than l-enantiomer-incorporated ASCs [(l-Phe), (l-1Nal), and (l-2Nal)ASC]. Structural comparison of the two analogues containing isomeric naphthyl groups showed that the 1-naphthyl isomer induced a more stable open structure than the 2-naphthyl isomer. In particular, [d-1Nal]ASC showed the most significant transformation from the folded to the open structure in solution, and exhibited the strongest cytotoxicity toward HL-60 cells.
authors: Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka, 569-1094, Japan.
authors: Akiko
authors: A
authors: Asano
authors: Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka, 569-1094, Japan.
authors: Katsuhiko
authors: K
authors: Minoura
authors: Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka, 569-1094, Japan.
authors: Takeshi
authors: T
authors: Yamada
authors: Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka, 569-1094, Japan.
authors: Mitsunobu
authors: M
authors: Doi
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D008958:Models, Molecular; D009281:Naphthalenes / Q000737:chemistry*; D010080:Oxazoles / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D010649:Phenylalanine / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry
chemical_list: D003603:Cytotoxins; D009281:Naphthalenes; D010080:Oxazoles; D010456:Peptides, Cyclic; D013844:Thiazoles; D010649:Phenylalanine; C059031:1-naphthylalanine; C075813:ascidiacyclamide; D000409:Alanine; C513002:2-naphthylalanine
keywords: 1H NMR; CD spectrum; ROESY; ascidiacyclamide; crystal structure; cytotoxicity; enantiomer; naphthylalanine; phenylalanine; ring-current effect; structural isomer