XTEN™ is a class of unstructured hydrophilic, biodegradable protein polymers designed to increase the half-lives of therapeutic peptides and proteins. XTEN polymers and XTEN fusion proteins are typically expressed in Escherichia coli and purified by conventional protein chromatography as monodisperse polypeptides of exact length and sequence. Unstructured XTEN polypeptides have hydrodynamic volumes significantly larger than typical globular proteins of similar mass, thus imparting a bulking effect to the therapeutic payloads attached to them. Since their invention, XTEN polypeptides have been utilized to extend the half-lives of a variety of peptide- and protein-based therapeutics. Multiple clinical and preclinical studies and related drug discovery and development efforts are in progress. This review details the most current understanding of physicochemical properties and biological behavior of XTEN and XTENylated molecules. Additionally, the development path and status of several advanced drug discovery and development efforts are highlighted.

The placement of fluorophores in close proximity to metal nanoparticle surfaces is proposed to enhance several photo-physical properties of the dyes, potentially leading to improved quantum yields and decreased photobleaching. It is difficult in practice, however, to establish and maintain the nanoscale distances that are required to maximize these effects. The type of metal, size, and shape of the nanoparticle, the physical distance separating the metal nanoparticle from the organic dye, and the spectral properties of the fluorophore itself are all proposed to influence the quantum yield and lifetime. This results in a complex behavior that can lead to either enhanced or quenched fluorescence in different contexts. In this report, we describe a well-defined system that can be used to explore these effects, while physically preventing the fluorophores from contacting the nanoparticle surfaces. The basis of this system is the spherical protein capsid of bacteriophage MS2, which was used to house gold particles within its interior volume. The exterior surface of each capsid was then modified with Alexa Fluor 488 (AF 488) labeled DNA strands. By placing AF 488 dyes at distances of 3 bp, 12 bp, and 24 bp from the surface of capsids containing 10 nm gold nanoparticles, fluorescence intensity enhancements of 2.2, 1.2, and 1.0 were observed, respectively. A corresponding decrease in fluorescence lifetime was observed for each distance. Due to its well-defined and modular nature, this architecture allows the rapid exploration of the many variables involved in metal-controlled fluorescence, leading to a better understanding of this phenomenon.

We present a supported membrane platform consisting of a fluid lipid bilayer membrane embedded with a fixed array of gold nanoparticles. The system is realized by preforming a hexagonal array of gold nanoparticles (∼5–7 nm) with controlled spacing (∼50–150 nm) fixed to a silica or glass substrate by block copolymer lithography. Subsequently, a supported membrane is assembled over the intervening bare substrate. Proteins or other ligands can be associated with the fluid lipid component, the fixed nanoparticle component, or both, providing a hybrid interface consisting of mobile and immobile components with controlled geometry. We test different biochemical coupling strategies to bind individual proteins to the particles surrounded by a fluid lipid membrane. The coupling efficiency to nanoparticles and the influence of nanoparticle arrays on the surrounding membrane integrity are characterized by fluorescence imaging, correlation spectroscopy, and super-resolution fluorescence microscopy. Finally, the functionality of this system for live cell experiments is tested using the ephrin-A1–EphA2 juxtacrine signaling interaction in human breast epithelial cells.

Closed reductions of displaced coronal fractures of the capitellum were successfully obtained for nine patients. The method involves spontaneous reduction by allowing the elbow to fully extend under anesthesia and then gradually flexing the elbow while distracting the elbow joint. Distraction allows the radial head to capture the capitellar fragment in the joint rather than push it proximally. The elbow is immobilized at 90 degrees for 3 weeks. Gentle active motion is then started. Closed reduction is often or usually obtained, but open reduction and internal fixation are performed in those cases in which a closed reduction cannot be obtained.