Catalytic asymmetric synthesis of meta benzene isosteres.

Although aromatic rings are common elements in pharmaceutically active compounds, the presence of these motifs brings several liabilities with respect to the developability of a drug. Nonoptimal potency, metabolic stability, solubility and lipophilicity in pharmaceutical compounds can be improved by replacing aromatic rings with non-aromatic isosteric motifs. Moreover, whereas aromatic rings are planar and lack three-dimensionality, the binding pockets of most pharmaceutical targets are chiral.

Bicyclic Caged Morpholino Oligonucleotides for Optical Gene Silencing.

Caged morpholino oligonucleotides (cMOs) are synthetic tools that allow light-inducible gene silencing in live organisms. Previously reported cMOs have utilized hairpin, duplex, and cyclic structures, as well as caged nucleobases. While these antisense technologies enable efficient optical control of RNA splicing and translation, they can have limited dynamic range.

Visible-Light-Activated High-Density Materials for Controlled in Vivo Insulin Release.

In this work, we describe the synthesis, characterization, and ultimate in vivo assessment of second-generation insulin photoactivated depot (PAD) materials. These are the first to use visible light to stimulate insulin release and have an in vivo performance that is 28-fold improved relative to first-generation materials. This improvement is due to two major factors linked to the utilized chemistry: (1) we have incorporated the coumarin photocleavable group, which increases the photorelease wavelength into the visible range, enhancing tissue penetration of the light; (2) phototoggling of insulin solubility is produced by linking three insulin molecules to a central bridge via light cleaved groups, and not by bonding to a large polymer.

Hydrophobic Tags for Highly Efficient Light-Activated Protein Release.

We have previously described the photoactivated depot (PAD) approach for the light-stimulated release of therapeutic proteins such as insulin. The aim of this method is to release insulin from a shallow dermal depot in response to blood glucose information, using transcutaneous irradiation. Our first approach utilized a photocleavable group that linked insulin to an insoluble but injectable polymer bead.

Light Control of Insulin Release and Blood Glucose Using an Injectable Photoactivated Depot.

In this work we demonstrate that blood glucose can be controlled remotely through light stimulated release of insulin from an injected cutaneous depot. Human insulin was tethered to an insoluble but injectable polymer via a linker, which was based on the light cleavable di-methoxy nitrophenyl ethyl (DMNPE) group. This material was injected into the skin of streptozotocin-treated diabetic rats.

Macromol. Biosci. 8/2016.

Back Cover: The authors have created polymers which release insulin using light. These materials utilize insulin itself as the primary monomer and therefore achieve a very high density (85% w/w insulin). This near perfect density makes them ideal as photoactivated depots of insulin.

Polymerizing Insulin with Photocleavable Linkers to Make Light-Sensitive Macropolymer Depot Materials.

The use of light-sensitive polymers for the release of therapeutics is an important approach allowing the timing and amount of the release to be controlled precisely. The use of light has been pioneered to control insulin release from a dermal photoactivated depot, or PAD. One of the main impediments to the use of light-sensitive polymers in this context is the density of the materials: The large majority of the material is the carrier polymer, with the minority being the therapeutic.