Synthetic multifunctional pores with external and internal active sites for ligand gating and noncompetitive blockage.
Design, synthesis, and multifunctionality of p-octiphenyl beta-barrel pores with external LRL triads and internal HH dyads are described. Molecular recognition of anionic fullerenes > calixarenes > pyrenes by guanidinium arrays at the outer pore surface is shown to result in pore opening, whereas alpha-helix recognition within the topologically matching internal space is shown to result in noncompetitive pore blockage. This experimental evidence for multifunctionality is supported by comparison with pertinent control pores and blockers, by structural studies using FRET from p-octiphenyl donors in the pore to BODIPY acceptors in the bilayer, and by molecular mechanics simulations. Practical usefulness of ligand-gated synthetic multifunctional pores is exemplified with the continuous detection of chemical processes.
Gorteau
Virginie
V
Department of Organic Chemistry, University of Geneva, Geneva, Switzerland.
Perret
Florent
F
Bollot
Guillaume
G
Mareda
Jiri
J
Lazar
Adina N
AN
Coleman
Anthony W
AW
Tran
Duy-Hien
DH
Sakai
Naomi
N
Matile
Stefan
S
D000818:Animals; D001665:Binding Sites; D001896:Boron Compounds / Q000737:chemistry; D004950:Esterases / Q000737:chemistry / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D008024:Ligands; D008051:Lipid Bilayers / Q000737:chemistry*; D008099:Liver / Q000201:enzymology; D008567:Membranes, Artificial; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000737:chemistry*; D013552:Swine
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D008024:Ligands; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D010455:Peptides; C015462:polyarginine; D011099:Polyglutamic Acid; D004950:Esterases