Synthesis of Biomimetic Channels with Amphiphilic Cyclodextrins:

1. Artificial channels Natural channels Crown ethers: Lehn and coll., Tetrahedron lett. 1988 Resorcen: hemi-channels Kokube et al., Angew, 1994 Cyclic Peptides association Ghadiri et al., Nature, 1993 Anantimicrobial: The Gramicidine A Anionic channel: KcsA MacKinnon et al., Science, 1998 A toxin: α-hémolysine Song et al., Science, 1996 Aim of the work and tools… Biomimetic artificial channels Advantages of cyclodextrins Permanent channel • To increase our understanding of natural ion channels • Possible avenues to novel non natural antimicrobials How? Using cyclodextrins as pore-forming molecules hydrophobic • Compatible geometry with lipid bilayer • Variation of the pore size • Selective modification of the hydroxyl groups to form amphiphilic molecules hydrophilic hydrophilic hemi-channel (or transient channels) hydrophilic Hemi-channels synthesized from per-2,3-heptyl-β-CD (A) and per-6-PEO-2,3-heptyl- β-CD (B1 and B2): MALDI-TOF and 13C NMR characterizations of compound B1: Electrical measurements of various CD pores inserted in lipid bilayer membranes h, i, 6 A B1 B2 Measured current vs time for a negative voltage g j 3,5 a f k b cd e Water solubility improved by the PEO chains Formation of well-defined transient pores 1 2,4 Strategy to synthesize transmembranar channels ESI-MS and 2D NMR characterizations of compound C: A B C Compound C (per-2,6-di-O-hydroxypropyl-3-O-methyl-()-CD)obtained with good yields Synthesis of Biomimetic Channels with Amphiphilic Cyclodextrins: From Hemi to Transmembranar Channels Z. Eskandani, N. Badi, C. Huin, L. Auvray, P. Guégan, Laboratoire Matériaux Polymères aux Interfaces UMR CNRS 7581, Université d’Evry-Val-d’Essonne, 91025 Evry Cedex, France contact : pguegan@univ-evry.fr Conclusion and prospects 1) Formation of hemi-channels proved by electrical measurments 2) Transmembranar channels formation is expected with the further molecules obtainedfrom the ethylene oxide anionic polymerisation initiated by the per-2,6-di-O-hydroxypropyl-3-O-methyl-()-CD)