Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages.

Activation of liver X receptors (LXRs) with synthetic agonists promotes reverse cholesterol transport and protects against atherosclerosis in mouse models. Most synthetic LXR agonists also cause marked hypertriglyceridemia by inducing the expression of sterol regulatory element-binding protein (SREBP)1c and downstream genes that drive fatty acid biosynthesis. Recent studies demonstrated that desmosterol, an intermediate in the cholesterol biosynthetic pathway that suppresses SREBP processing by binding to SCAP, also binds and activates LXRs and is the most abundant LXR ligand in macrophage foam cells.

Seebach's conjunctive reagent enables double cyclizations.

When ketones flanked on both sides by nucleophilic atoms react with Seebach's nitropropenyl pivaloate reagent, direct couplings take place to give two new ring systems and three bonds. Cis-ring fusions are observed in unions leading to 5,5-, 5,6-, and 6,6-bicycles. Densely functionalized and rigid frameworks may be rapidly formed by the chemistry described herein.

Using steered molecular dynamics simulations and single-molecule force spectroscopy to guide the rational design of biomimetic modular polymeric materials.

This article describes results on using steered molecular dynamics (SMD) simulations and experimental single molecule force spectroscopy (SMFS) to investigate the relationship between hydrogen bonding and mechanical stability of a series of homodimeric β-sheet mimics. The dimers consisting of 4, 6, and 8 H-bonding sites were modeled in explicit chloroform solvent and the rupture force was studied using constant velocity SMD. The role of solvent structuring on the conformation of the dimers was analyzed and showed no significant contribution of chloroform molecules in the rupture event.

Synthesis and single-molecule studies of a well-defined biomimetic modular multidomain polymer using a peptidomimetic beta-sheet module.

In the pursuit of advanced biomaterials with combined strength, toughness, and elasticity, a new class of well-defined modular polymers has been synthesized, and their nanomechanical properties have been studied using atomic force microscopy. These polymers are based on a peptidomimetic beta-sheet-based double-closed loop (DCL) module, which was designed to overcome the limitation of the modular polymers we reported previously (J. Am.

Modular domain structure: a biomimetic strategy for advanced polymeric materials.

A long lasting challenge in polymer science is to design polymers that combine desired mechanical properties such as tensile strength, fracture toughness, and elasticity into one structure. A novel biomimetic modular polymer design is reported here to address this challenge. Following the molecular mechanism used in nature, modular polymers containing multiple loops were constructed by using precise and strong hydrogen bonding units.