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.
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.
Asano
Akiko
A
Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Yamada
Takeshi
T
Numata
Atsushi
A
Doi
Mitsunobu
M
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
D000596:Amino Acids; D003603:Cytotoxins; D010456:Peptides, Cyclic; C075813:ascidiacyclamide