The structure and properties of gold nanoparticles make them useful for a wide array of biological application. Toxicity, however, has been observed at high concentrations using these systems. MTT, hemolysis, and bacterial viability assays were used to explore differential toxicity among the cell types used, using 2 nm core particles. These studies show that cationic particles are moderately toxic, whereas anionic particles are quite nontoxic. Concentration-dependent lysis mediated by initial electrostatic binding was observed in dye release studies using lipid vesicles, providing the probable mechanism for observed toxicity with the cationic MMPCs.

Foldamers are sequence-specific oligomers akin to peptides, proteins and oligonucleotides that fold into well-defined three-dimensional structures. They offer the chemical biologist a broad pallet of building blocks for the construction of molecules that test and extend our understanding of protein folding and function. Foldamers also provide templates for presenting complex arrays of functional groups in virtually unlimited geometrical patterns, thereby presenting attractive opportunities for the design of molecules that bind in a sequence- and structure-specific manner to oligosaccharides, nucleic acids, membranes and proteins. We summarize recent advances and highlight the future applications and challenges of this rapidly expanding field.

Thioalkyl and thioalkylated oligo(ethylene glycol) (OEG) ligands with chain-end functionality were used to fabricate water-soluble CdSe nanoparticle scaffolds. Surface recognition of chymotrypsin (ChT) was achieved using these functionalized nanoparticle scaffolds, with three levels of interaction demonstrated: no interaction (OEG terminated with hydroxyl group), inhibition with denaturation (carboxylate-terminated thioalkyl ligands), and inhibition with retention of structure (carboxylate-terminated OEG). The latter process was reversible upon an increase in ionic strength, with essentially complete restoration of enzymatic activity.

Membrane protein orientation has traditionally been determined by NMR using mechanically or magnetically aligned samples. Here we show a new NMR approach that abolishes the need for preparing macroscopically aligned membranes. When the protein undergoes fast uniaxial rotation around the bilayer normal, the 0 degrees -frequency of the motionally averaged powder spectrum is identical to the frequency of the aligned protein whose alignment axis is along the magnetic field. Thus, one can use unoriented membranes to determine the orientation of the protein relative to the bilayer normal. We demonstrate this approach on the M2 transmembrane peptide (M2TMP) of influenza A virus, which is known to assemble into a proton-conducting tetrameric helical bundle. The fast uniaxial rotational diffusion of the M2TMP helical bundle around the membrane normal is characterized via 2H quadrupolar couplings, C-H and N-H dipolar couplings, 13C chemical shift anisotropies, and 1H T1rho relaxation times. We then show that 15N chemical shift anisotropy and N-H dipolar coupling measured on these powder samples can be analyzed to yield precise tilt angles and rotation angles of the helices. The data show that the tilt angle of the M2TMP helices depends on the membrane thickness to reduce the hydrophobic mismatch. Moreover, the orientation of a longer M2 peptide containing both the transmembrane domain and cytoplasmic residues is similar to the orientation of the transmembrane domain alone, suggesting that the transmembrane domain regulates the orientation of this protein and that structural information obtained from M2TMP may be extrapolated to the longer peptide. This powder-NMR approach for orientation determination is generally applicable and can be extended to larger membrane proteins.