The ability to monitor DNA polymerase activity with single-nucleotide resolution has been the cornerstone of a number of advanced single-molecule DNA sequencing concepts. Toward this goal, we report the first observation of the base-by-base DNA polymerase activity with single-base resolution at the single-molecule level. We describe the design and characterization of a supramolecular nanopore device capable of detecting up to nine consecutive DNA polymerase-catalyzed single-nucleotide primer extensions with high sensitivity and spatial resolution (
A new class of self-assembling peptides based on cyclic peptides made of alternating 3-aminocyclohexanecarboxylic acid (gamma-Acc) and alpha-amino acids is described. The studied cylindrical assemblies are models for a new class of self-assembling peptide nanotubes (SPN) that present the particular property of having the C2 methylene group pointing toward the lumen of the cavity, modifying the properties of the inner surface of the assembly.
In this study, we describe the self-assembling properties of cyclic peptides containing g-amino acids in lipid bilayers to form transmembrane nanotubes. The resulting ion channel models are selective for alkaline ions. Although the transport rates conform to the lyotropic series, these partially hydrophobic channels show an unexpectedly higher rate for sodium ions.
Diverse virus families have evolved to exploit the acidification of endosomal compartments to gain entry into cells. We describe a supramolecular approach for selectively targeting and inhibiting viral infections through this central biochemical pathway. Using adenovirus as a model non-enveloped virus, we have determined that an eight-residue cyclic D,L-alpha-peptide, selected from a directed combinatorial library, can specifically prevent the development of low pH in endocytic vesicles, arrest the escape of virions from the endosome, and abrogate adenovirus infection without an apparent adverse effect on cell viability. The likely generality of this approach against other pH-dependent viral infections is supported by the inhibition of type-A influenza virus escape from endosomes in the presence of the same peptide. Our studies suggest that self-assembling cyclic D,L-alpha-peptides hold considerable potential as a new rational supramolecular approach toward the design and discovery of broad-spectrum antiviral agents.
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