trans-2-Aminocyclohexanols as pH-triggered molecular switches

BIOL 170

Barbora Brazdova, b_brazdova@pacific.edu1, Sombo Koo, vsamoshin@pacific.edu1, Yuen Shan Wong, b_brazdova@pacific.edu1, Andrey V. Samoshin, vsamoshin@pacific.edu1, Ningrong Zhang, n_zhang@pacific.edu2, Andreas H. Franz, afranz@pacific.edu1, Xin Guo, xguo@pacific.edu2, and Vyacheslav V. Samoshin, vsamoshin@pacific.edu1. (1) Department of Chemistry, University of the Pacific, 3601 Pacific Ave., Stockton, CA 95211, (2) Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, 3601 Pacific Ave., Stockton, CA 95211
The cyclohexane-based conformationally controlled molecular switches provide a new and promising approach to allosteric systems with negative cooperativity. Protonation of trans-2-aminocyclohexanols leads to dramatic conformational changes: due to a strong intramolecular hydrogen bond, a conformer with equatorial ammonio- and hydroxy-groups becomes predominant. This ‘impulse' is mechanically transmitted by the structure of the molecule to induce a conformational change of a remote site, thus altering its properties. Thus, these structures can serve as powerful conformational pH-triggers. The variation of NR2 groups allows a broad tuning of the conformational equilibrium, which was studied by NMR. Heterotropic allosteric systems with high negative cooperativity may find many applications, e.g in the triggerable lipid vesicles for drug and gene delivery.

 

Chemistry and Metabolism
4:30 PM-6:30 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Division of Biological Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006