Oral Presentation 10th Australian Peptide Conference 2013

Homo- and mixed oligomers based on a constrained bicyclic β-amino acid to support helical diversity (#59)

Muriel Amblard 1 , Baptiste Legrand 1 , Christophe André 1 , Laure Moulat 1 , Emmanuel Wenger 2 , Claude Didierjean 2 , Marie-Christine Averlant-Petit 3 , Jean Martinez 1 , Monique Calmès 1
  1. Institut des Biomolécules Max Mousseron, Montpellier, France
  2. Laboratoire de Cristallographie, Résonance Magnétique et Modélisation Moléculaire, CNRS UMR 7036, Vandoeuvre-lès-Nancy Cedex, France
  3. Laboratoire de Physique Chimie-Macromoléculaire, CNRS UMR 7568, Nancy Cedex, France

Foldamers are non-natural oligomers able to adopt well-defined conformations, stabilized by non-covalent interactions, often inspired by natural compounds.1  By mimicking the shapes of natural polymers such as peptides, proteins or nucleic acids, they became attractive tools for designing molecules with specific function and potential biomedical applications. For example, they can be putative cell penetrating compounds, protein-protein interactions modulators or can present antimicrobial activities. In this context, derivatives of α-amino acids such as β- and γ-amino acids have received much attention for the construction of artificial architectures able to display a large diversity of helical structures (i.e. 14-, 12, 10/12-helix,…). These helical systems were substantially enlarged with the use of homo- and heterochiral constrained cyclic derivatives and/or with the combination of α-, β- and γ- amino acids to synthesize α/β, α/γ, β/γ sequences of particular folding.2

In this work, we explored the ability of homo- and mixed oligomers incorporating a highly constrained bicyclic β-amino acid [(S)-aminobicyclo[2.2.2]octane-2-carboxylic acid] [(S)-ABOC],3,4   to induce a broad range of stable and predictable helical structures.

Different oligomers using amide or urea linkages and various alternating α-amino-acid and β3-homo-amino acid sequences have been generated.5  Their synthesis and their structural characterizations conducted by circular dichroism (CD), X-ray diffraction crystallography (XRD), nuclear magnetic resonance (NMR) and molecular modeling will be presented.

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  1. S. H. Acc. Chem. Res. 1998, 31, 173-180; Hill, D. J.; Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore, J. S. Chem. Rev. 2001, 101, 3893-4011; Cheng, R. P.; Gellman, S. H.; DeGrado, W. F. Chem. Rev. 2001, 101, 3219-3232; Seebach, D.; Beck, A. K.; Bierbaum, D. J. Chem Biodivers 2004, 1, 1111-1239; Goodman, C. M.; Choi, S.; Shandler, S.; DeGrado, W. F. Nat. Chem. Biol. 2007, 3, 252-262; Martinek, T. A.; Fulop, F. Chem. Soc. Rev. 2012, 41, 687-702.
  2. Horne, W. S.; Gellman, S. H. Acc. Chem. Res. 2008, 41, 1399-1408; Vasudev, P. G.; Chatterjee, S.; Shamala, N.; Balaram, P. Chem. Rev. 2011, 111, 657-687
  3. Songis O., Didierjean C., Laurent C., Martinez J., Calmes M. (2007), Eur. J. Org. Chem. 3166–3172.
  4. André C., Legrand B., Deng C., Didierjean C., Pickaert G., Martinez J., Averlant-Petit M.C., Amblard M., Calmes M. (2012), Org Lett., 17;14(4):960-3.
  5. Legrand B., André C., Wenger E., Didierjean C., Averlant-Petit M.C., Martinez J., Calmes M., Amblard M. (2012), Angew Chem Int Ed Engl., 5;51(45):11267-70. Legrand B., André C., Moulat L., Wenger E., Didierjean C., Aubert E., Averlant-Petit M.C., Martinez J., Amblard M., Calmes M. (2013), Submitted.