Conformational transformation of ascidiacyclamide analogues induced by incorporating enantiomers of phenylalanine, 1‐naphthylalanine or 2‐naphthylalanine. (March 2016)

• Record Type: Journal Article
• Authors: Asano, Akiko; Minoura, Katsuhiko; Yamada, Takeshi; Doi, Mitsunobu
• Is Part Of: Journal of peptide science. Volume 22:Number 3(2016:Mar.)
• Page Start: 156
• Page End: 165
• Publication Date: 2016-03
• Subjects: ascidiacyclamide -- phenylalanine -- naphthylalanine -- structural isomer -- enantiomer -- crystal structure -- 1H NMR -- ROESY -- ring‐current effect -- CD spectrum -- cytotoxicity; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.2853
• Languages: English
• ISSNs: 1075-2617

Abstract

Abstract : 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 ‐)] incorporatingl ‐1‐naphthylalanine (l ‐1Nal), l ‐2‐naphthylalanine (l ‐2Nal), d ‐phenylalanine (d ‐Phe), d ‐1‐naphthylalanine (d ‐1Nal) ord ‐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 thatd ‐enantiomer‐incorporated ASCs [(d ‐Phe), (d ‐1Nal), and (d ‐2Nal)ASC] transformed from the folded to the open structure in solution more easily thanl ‐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. Abstract : Ascidiacyclamide analogues incorporated enantiomers of phenylalanine, 1‐naphtylalanine or 2‐naphthylalanine were designed. Structural analyses suggested thatd ‐enantiomer‐incorporated ASCs transformed from the folded to the open structure more easily thanl ‐enantiomer‐incorporated ASCs. In particular, incorporating thed ‐1Nal residue stabilized the open structure, resulting in the strongest cytotoxicity.