Synthesis and characterisation of helical beta-peptide architectures that contain (S)-beta3-HDOPA(Crown Ether) derivatives

• Published in: Chemistry : a European journal 2008, Vol.14 (10), p.3154-3163
• Main Authors: Dutot, Laurence, Gaucher, Anne, Elkassimi, Khadidja, Drapeau, Jeremy, Wakselman, Michel, Mazaleyrat, Jean-Paul, Peggion, Cristina, Formaggio, Fernando, Toniolo, Claudio
• Format: Article
• Language: English
• Subjects: Circular Dichroism - methods; Crown Ethers - chemistry; Dihydroxyphenylalanine - chemistry; Magnetic Resonance Spectroscopy - methods; Magnetic Resonance Spectroscopy - standards; Molecular Structure; Peptides - chemical synthesis; Peptides - chemistry; Protein Structure, Secondary; Reference Standards; Spectroscopy, Fourier Transform Infrared - methods; Stereoisomerism
• ISSN: 0947-6539
• 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.