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Conformational change of ascidiacyclamide caused by asymmetric modification for an isoleucine residue: Structural analyses of [Gly], [Leu], and [Phe]ascidiacyclamides by X-ray diffraction and NMR spectroscopy

✍ Scribed by Mitsunobu Doi; Fumiyoshi Shinozaki; Yasuko In; Toshimasa Ishida; Daisuke Yamamoto; Miyoko Kamigauchi; Makiko Sugiura; Yasumasa Hamada; Kohfuku Kohda; Takayuki Shioiri


Publisher
Wiley (John Wiley & Sons)
Year
1999
Tongue
English
Weight
173 KB
Volume
49
Category
Article
ISSN
0006-3525

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✦ Synopsis


Ascidiacyclamide, a cytotoxic cyclic peptide from tunicate, is composed of unusual amino acids and has a repeated sequence, c[-thiazole-D-Valoxazoline-L-Ile-] 2 ([Ile]ASC). The symmetric chemical structure has been assumed to be correlated with the cytotoxicity, and it is reasonable to consider that the disturbance of its structure from the C 2 symmetry results in the changes of conformation and activity. In order to quantitatively estimate the molecular conformation-activity relationship, an isoleucine residue was substituted by Gly, Leu, or Phe to disturb the C 2 symmetry. The conformations of three derivatives were examined by nmr spectroscopy and the crystal structure of [Leu]ASC was also analyzed by x-ray diffraction method.