Incorporation of unprotected heterocyclic side chains into peptoid oligomers via solid-phase submonomer synthesis.

Peptoids (N-substituted glycines) are an important class of biomimetic oligomers that have made a significant impact in the areas of combinatorial drug discovery, gene therapy, drug delivery, and biopolymer folding in recent years. Sequence-specific peptoid oligomers are easily assembled from primary amines by the solid-phase submonomer method. However, most amines that contain heterocyclic nitrogens in the side chain do not incorporate efficiently.

Toward the synthesis of artificial proteins: the discovery of an amphiphilic helical peptoid assembly.

While nature exploits folded biopolymers to achieve molecular recognition and catalysis, comparable abiological heteropolymer systems have been difficult to create. We synthesized and identified abiological peptoid heteroploymers capable of binding a dye. Using combinatorial synthesis, we constructed a library of 3400 amphiphilic 15-mer peptoids on an ultra-high-capacity beaded support.

Two-dimensional structure of beta-amyloid(10-35) fibrils.

Beta-amyloid (Abeta) peptides are the main protein component of the pathognomonic plaques found in the brains of patients with Alzheimer's disease. These heterogeneous peptides adopt a highly organized fibril structure both in vivo and in vitro. Here we use solid-state NMR on stable, homogeneous fibrils of Abeta(10-35).

Transdermal and transmucosal powdered drug delivery.

High-velocity powder injection is a promising new drug-delivery technique that provides needle- and pain-free delivery of traditional drugs, drugs from biotechnology such as proteins, peptides, and oligonucleotides as well as traditional and genetic vaccines. The energy of a transient helium gas jet accelerates fine drug particles of 20 microns-100 microns diameter to high velocities and delivers them into skin or mucosal sites. This review describes the configuration and operating principles of devices that accelerate the particles, the required properties of the particles, the characteristics of the target tissues, and features of the developmental test methods.

Dipolar recoupling NMR of biomolecular self-assemblies: determining inter- and intrastrand distances in fibrilized Alzheimer's beta-amyloid peptide.

We demonstrate a new method for investigating the structure of self-associating biopolymers using dipolar recoupling NMR techniques. This approach was applied to the study of fibrillar beta-amyloid (Abeta) peptides (the primary component of the plaques of Alzheimer's disease) containing only a single isotopic spin label (13C), by employing the DRAWS (dipolar recoupling with a windowless sequence) technique to measure 13C-13C distances. The 'single-label' approach simplified analysis of DRAWS data, since only interstrand contacts are present, without the possibility of any intrastrand contacts.