Gorteau Virginie, Bollot Guillaume, Mareda Jiri, Pasini Dario, Tran Duy-Hien, Lazar Adina N, Coleman Anthony W, Sakai Naomi, Matile Stefan
Department of Organic Chemistry, University of Geneva, Geneva, Switzerland.
Bioorg Med Chem. 2005 Sep 1;13(17):5171-80. doi: 10.1016/j.bmc.2005.05.022.
Studies on synthetic multifunctional pores with external and internal active sites for ligand gating and noncompetitive blockage are presented, with emphasis on the contribution of external ligands to the characteristics of pore. A comparison between different synthetic multifunctional pores reveals that the location of functional groups in rigid-rod beta-barrel pores is precisely reflected in the function: molecular recognition at the outer barrel surface results in pore opening, while molecular recognition at the inner barrel surface results in pore closing. Negligible nonspecific leakage, disappearance of pH gating, inhibition of intervesicular pore transfer, and maybe also the flickering of currents of single open pores characterize external ligands as adhesive cushions that liberate the pore from lateral pressure exerted by the surrounding membrane. Refined molecular models show good agreement with pore design and experimental facts with regard to function.
本文介绍了对具有外部和内部活性位点以实现配体门控和非竞争性阻断的合成多功能孔的研究,重点关注外部配体对孔特性的贡献。不同合成多功能孔之间的比较表明,刚性棒状β-桶状孔中官能团的位置在功能上得到了精确体现:外桶表面的分子识别导致孔开放,而内桶表面的分子识别导致孔关闭。可忽略不计的非特异性泄漏、pH门控的消失、泡间孔转移的抑制,以及可能还有单个开放孔电流的闪烁,这些都将外部配体表征为粘性垫层,使孔免受周围膜施加的侧向压力。精细的分子模型在功能方面与孔设计和实验事实显示出良好的一致性。