title: Cyclo(-Cha-Oxz-D-Val-Thz-Ile-Oxz-D-Val-Thz-) N,N-dimethylacetamide dihydrate: a square form of cyclohexylalanine-incorporated ascidiacyclamide having the strongest cytotoxicity.
abstract: The title compound, 1-cyclohexylmethyl-1-de(1-methylpropyl)ascidiacyclamide N,N-dimethylacetamide dihydrate, C(39)H(56)N(8)O(6)S(2) x C(4)H(9)NO x 2H(2)O, a cyclohexylalanine-incorporated ascidiacyclamide analogue ([Cha]ASC), shows a square form similar to natural ASC. On the other hand, CD (circular dichroism) spectra showed [Cha]ASC to have a folded structure in solution, making it the second known analogue to show a discrepancy between its crystal and solution structures. Moreover, the cytotoxicity of [Cha]ASC (ED(50) = 5.6 micro g ml(-1)) was approximately two times stronger than that of natural ASC or a related phenylalanine-incorporated analogue, viz. cyclo(-Phe-Oxz-D-Val-Thz-Ile-Oxz-D-Val-Thz-) ([Phe]ASC), and was confirmed to be associated with the square form. However, [Phe]ASC was previously shown to be folded in the crystal structure, which suggests that the difference between the aromatic and aliphatic rings affects the molecular folding of the ASC molecule.
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Asano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Numata
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Doi
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology*; D017510:Protein Folding
chemical_list: D000596:Amino Acids; D003603:Cytotoxins; D010456:Peptides, Cyclic; C075813:ascidiacyclamide