Dutot Laurence, Gaucher Anne, Elkassimi Khadidja, Drapeau Jeremy, Wakselman Michel, Mazaleyrat Jean-Paul, Peggion Cristina, Formaggio Fernando, Toniolo Claudio
ILV, UMR CNRS 8180, University of Versailles, 78035 Versailles, France.
Chemistry. 2008;14(10):3154-63. doi: 10.1002/chem.200701360.
A new set of beta-amino acids that carry various crown ether receptors on their side chains of the general formula (S)-beta(3)-HDOPA(crown ether) (HDOPA: homo-3,4-dihydroxyphenylalanine; (crown ether): [15]crown-5 ([15-C-5]), [18]crown-6 ([18-C-6]), [21]crown-7 ([21-C-7]), 1,2-Benzo-[24]crown-8 ([Benzo-24-C-8]) and (R)-Binol-[20]crown-6 ([(R)-Binol-20-C-6])) was prepared. Peptides that are based on these new crowned beta-amino acids combined with (1S,2S)-ACHC (2-aminocyclohexanecarboxylic acid), which is known to be a potent 3(14)-helix inducer, to the hexamer level, with two crowned residues at the i and i+3 positions of the main-chain, were synthesized in solution by stepwise coupling using Boc-N(alpha)-protection (Boc: tert-butoxycarbonyl) and the EDC/HOAt C-activation method. Their conformational analysis was performed by using FTIR absorption, NMR and CD spectroscopy techniques. Our results are in full agreement with a 3(14)-helix conformation.
制备了一组新的β-氨基酸，其侧链带有各种冠醚受体，通式为(S)-β(3)-HDOPA(冠醚)（HDOPA：高3,4-二羟基苯丙氨酸；(冠醚)：[15]冠-5([15-C-5])、[18]冠-6([18-C-6])、[21]冠-7([21-C-7])、1,2-苯并-[24]冠-8([苯并-24-C-8])和(R)-联萘酚-[20]冠-6([(R)-联萘酚-20-C-6])）。基于这些新的冠醚化β-氨基酸与(1S,2S)-ACHC（2-氨基环己烷羧酸）（已知是一种有效的3(14)-螺旋诱导剂）组合而成的肽，在溶液中通过使用Boc-N(α)-保护（Boc：叔丁氧羰基）和EDC/HOAt C-活化方法逐步偶联至六聚体水平，主链的i和i+3位置有两个冠醚化残基。通过傅里叶变换红外吸收、核磁共振和圆二色光谱技术对其进行构象分析。我们的结果与3(14)-螺旋构象完全一致。
