Conformational transformation of ascidiacyclamide analogues induced by incorporating enantiomers of phenylalanine, 1‐naphthylalanine or 2‐naphthylalanine |
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| Authors: | Akiko Asano Katsuhiko Minoura Takeshi Yamada Mitsunobu Doi |
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| Affiliation: | Osaka University of Pharmaceutical Sciences, Osaka, Japan |
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| Abstract: | We designed five ascidiacyclamide analogues [cyclo(‐Xxx1‐oxazoline2‐d ‐Val3‐thiazole4‐l ‐Ile5‐oxazoline6‐d ‐Val7‐thiazole8‐)] 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 Xxx1 position of the peptide. The conformations of these analogues were then examined using 1H 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. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. |
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| Keywords: | ascidiacyclamide phenylalanine naphthylalanine structural isomer enantiomer crystal structure 1H NMR ROESY ring‐current effect CD spectrum cytotoxicity |
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