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Conformational transformation of ascidiacyclamide analogues induced by incorporating enantiomers of phenylalanine, 1‐naphthylalanine or 2‐naphthylalanine
Author(s) -
Asano Akiko,
Minoura Katsuhiko,
Yamada Takeshi,
Doi Mitsunobu
Publication year - 2016
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2853
Subject(s) - enantiomer , phenylalanine , transformation (genetics) , chemistry , stereochemistry , biochemistry , amino acid , gene
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. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.