Recyclable Metallic Imidazolium-Based Ionic Liquid-Catalyzed Selective Mono- and Double-Hydroboration in Water

The recyclable metallic imidazolium-based ionic liquid-catalyzed mono-hydroboration of imines, double-hydroboration of imine with aldehyde, and double-hydroboration of aniline with glutaric dialdehyde in the presence of HBpin in water is described for the first time. The ionic liquid [BMIm][FeCl4] showed excellent activity, high selectivity, and good recyclability for the catalytic imine hydroborations. This catalytic system widely tolerated various functional rings and unsaturated groups without additional reduction. Furthermore, the metallic ionic liquid [BMIm][FeCl4] could be reused for more than 15 runs in water without decay of the catalytic activity

TYY cyclic peptide inhibits ephrinA5 AP binding to immobilized EphA4 Fc fusion protein.

<p>The KYL peptide was used as a positive control at a concentration of 25 μM. The histogram shows the inhibition of ephrinA5 AP bound to EphA4 in the presence of KYL or TYY at different concentrations. Error bars represent standard errors from three independent measurements.</p

Binding mode of TYY with EphA4 receptor.

<p>(A) 2D interactions between the TYY cyclic peptide and the EphA4 receptor (by LigPlot). Residues with purple bonds in blue labels are from the ligand TYY peptide; residues with brown bonds in red labels are from EphA4. The green dashed line represents a potential hydrogen bond and its length. (B) 3D interactions between the TYY cyclic peptide and the EphA4 receptor (by Pymol). This model was generated by Autodock4, based on the crystal structure of EphA4 in complex with ephrinA2 (PDB: 2WO3). The TYY cyclic peptide is shown as a stick model with grey representing carbon atoms, red representing oxygen atoms and blue representing nitrogen atoms. The EphA4 is shown as a cyan ribbon with key residues shown as yellow sticks. Black dashed lines represent the hydrogen bonds.</p

Superposition of the TYY cyclic peptide with the ephrinA2 G-H loop region from the crystal structure of its complex with the EphA4 receptor (by Pymol, PDB: 2WO3).

<p>The TYY cyclic peptide is shown as a grey stick model, and ephrinA2 G-H loop region is shown as green stick model with red representing oxygen atoms and blue representing nitrogen atoms. The EphA4 is shown as a cyan ribbon. </p

Effects of the TYY cyclic peptide on viability of HUVEC cells.

<p>The HUVECs were treated with the indicated concentrations of the TYY peptide. A 0.1% DMSO control was used because the highest concentration of the DMSO vehicle in the TYY solutions was 0.1%. The cell viability was determined by CellTiter-Blue assays 24 h and 48 h after addition of TYY. Each experimental data point was generated from at least three independent experiments.</p

Design and Synthesis of Potent Bivalent Peptide Agonists Targeting the EphA2 Receptor

Designing potent and selective peptides and small molecules that target Eph receptor tyrosine kinases remains a challenge, and new strategies are needed for developing novel and potent ligands for these receptors. In this study, we performed a structure–activity relationship study of a previously identified 12 amino acid-long peptide, SWL, by alanine scanning to identify residues important for receptor binding. To further enhance and optimize the receptor binding affinity of the SWL peptide, we applied the concept of bivalent ligand design to synthesize several SWL-derived dimeric peptides as novel ligands capable of binding simultaneously to two EphA2 receptor molecules. The dimeric peptides possess higher receptor binding affinity than the original monomeric SWL peptide, consistent with bivalent binding. The most potent dimeric peptide, a SWL dimer with a six-carbon linker, has about 13-fold increased potency as compared to SWL. Furthermore, similar to SWL, the dimeric peptide is an agonist and can promote EphA2 tyrosine phosphorylation (activation) in cultured cells