A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys.

Obesity, defined as body mass index greater than 30, is a leading cause of morbidity and mortality and a financial burden worldwide. Despite significant efforts in the past decade, very few drugs have been successfully developed for the treatment of obese patients. Biological differences between rodents and primates are a major hurdle for translation of anti-obesity strategies either discovered or developed in rodents into effective human therapeutics.

Dynamic in vivo biocompatibility of angiogenic peptide amphiphile nanofibers.

Biomaterials that promote angiogenesis have great potential in regenerative medicine for rapid revascularization of damaged tissue, survival of transplanted cells, and healing of chronic wounds. Supramolecular nanofibers formed by self-assembly of a heparin-binding peptide amphiphile and heparan sulfate-like glycosaminoglycans were evaluated here using a dorsal skinfold chamber model to dynamically monitor the interaction between the nanofiber gel and the microcirculation, representing a novel application of this model. We paired this model with a conventional subcutaneous implantation model for static histological assessment of the interactions between the gel and host tissue.

Bioactive nanofibers instruct cells to proliferate and differentiate during enamel regeneration.

During tooth development, ectoderm-derived ameloblast cells create enamel by synthesizing a complex protein mixture serving to control cell to matrix interactions and the habit of hydroxyapatite crystallites. Using an in vitro cell and organ culture system, we studied the effect of artificial bioactive nanostructures on ameloblasts with the long-term goal of developing cell-based strategies for tooth regeneration. We used branched peptide amphiphile molecules containing the peptide motif Arg-Gly-Asp, or "RGD" (abbreviated BRGD-PA), known to self-assemble in physiologic environments into nanofibers that display on their surfaces high densities of this biological signal.

Sorting carbon nanotubes by electronic structure using density differentiation.

The heterogeneity of as-synthesized single-walled carbon nanotubes (SWNTs) precludes their widespread application in electronics, optics and sensing. We report on the sorting of carbon nanotubes by diameter, bandgap and electronic type using structure-discriminating surfactants to engineer subtle differences in their buoyant densities. Using the scalable technique of density-gradient ultracentrifugation, we have isolated narrow distributions of SWNTs in which >97% are within a 0.

Nitric oxide and nanotechnology: a novel approach to inhibit neointimal hyperplasia.

Objective: Nitric oxide (NO) has been shown to inhibit neointimal hyperplasia after arterial interventions in several animal models. To date, however, NO-based therapies have not been used in the clinical arena. Our objective was to combine nanofiber delivery vehicles with NO chemistry to create a novel, more potent NO-releasing therapy that can be used clinically.

Heparin binding nanostructures to promote growth of blood vessels.

Controlling new blood vessel formation is of interest in regenerative medicine and cancer treatment. Heparin, a biopolymer that binds to angiogenic growth factors, was used to nucleate the self-assembly of nanostructures from designed peptide amphiphile molecules. This process yields rigid nanofibers that display heparin chains to orient proteins for cell signaling.

Presentation of RGDS epitopes on self-assembled nanofibers of branched peptide amphiphiles.

Branched peptide amphiphile (PA) molecules bearing biological epitopes were designed and synthesized using orthogonal protecting group chemistry on amine groups at lysine residues. These molecules self-assemble into high-aspect-ratio cylindrical nanofibers, and their branched architecture enhances accessibility of epitopes for protein binding and also allows the presentation of more than one epitope in a single molecule. The RGDS cell adhesion epitope was used as a model bioactive signal on PA molecules for potential biomedical applications.

Presentation and recognition of biotin on nanofibers formed by branched peptide amphiphiles.

A branched peptide amphiphile system was designed for enhanced recognition of biotin on nanofibers formed by self-assembly of these molecules. Branching at a lysine residue was used to design peptide amphiphiles that are capable of presenting more than one epitope per molecule. We found that biotinylated branched structures form nanofibers that enhance recognition by the avidin protein receptor relative to similar nanostructures formed by linear peptide analogues.

Self-assembly and luminescence of oligo(p-phenylene vinylene) amphiphiles.

We have synthesized a series of amphiphilic molecules consisting of oligo(phenylene vinylene) (OPV) asymmetrically end-substituted with a hydrophilic poly(ethylene glycol) (PEG) segment and a hydrophobic alkyl chain. This amphiphilic structure induces self-assembly into both thermotropic and lyotropic lamellar liquid crystalline (LC) phases. The molecules form strongly fluorescent, self-supporting gels in both water and polar organic solvents, even at high concentrations on the order of 30 wt %.

Synthesis, self-assembly, and characterization of supramolecular polymers from electroactive dendron rodcoil molecules.

We report here the synthesis and self-assembly of a series of three molecules with dendron rodcoil architecture that contain conjugated segments of oligo(thiophene), oligo(phenylene-vinylene), and oligo(phenylene). Despite their structural differences, all three molecules yield similar self-assembled structures. Electron and atomic force microscopy reveals the self-assembly of the molecules into high aspect ratio ribbon-like nanostructures which at low concentrations induce gelation in nonpolar solvent.