Artificial transmembrane ion channels from self-assembling peptide nanotubes.
Naturally occurring membrane channels and pores are formed from a large family of diverse proteins, peptides and organic secondary metabolites whose vital biological functions include control of ion flow, signal transduction, molecular transport and production of cellular toxins. But despite the availability of a large amount of biochemical information about these molecules, the design and synthesis of artificial systems that can mimic the biological function of natural compounds remains a formidable task. Here we present a simple strategy for the design of artificial membrane ion channels based on a self-assembled cylindrical beta-sheet peptide architecture. Our systems--essentially stacks of peptide rings--display good channel-mediated ion-transport activity with rates exceeding 10(7) ions s-1, rivalling the performance of many naturally occurring counterparts. Such molecular assemblies should find use in the design of novel cytotoxic agents, membrane transport vehicles and drug-delivery systems.
Ghadiri
M R
MR
Department of Chemistry, Scripps Research Institute, La Jolla, California 92307.
Granja
J R
JR
Buehler
L K
LK
D000595:Amino Acid Sequence; D006860:Hydrogen Bonding; D007473:Ion Channels / Q000737:chemistry*; D017136:Ion Transport; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011522:Protons; D017550:Spectroscopy, Fourier Transform Infrared
D007473:Ion Channels; D008051:Lipid Bilayers; D008081:Liposomes; D010456:Peptides, Cyclic; D011522:Protons; C087234:cyclo((Trp-Leu)3-Gln-Leu)