Qingzhou Zhang

An In-tether Chiral Center Modulates the Helicity, Cell Permeability, and Target Binding Affinity of a Peptide.

The addition of a precisely positioned chiral center in the tether of a constrained peptide is reported, yielding two separable peptide diastereomers with significantly different helicity, as supported by circular dichroism (CD) and NMR spectroscopy. Single crystal X-ray diffraction analysis suggests that the absolute configuration of the in-tether chiral center in helical form is R, which is in agreement with theoretical simulations. The relationship between the secondary structure of the short peptides and their biochemical/biophysical properties remains elusive, largely because of the lack of proper controls. The present strategy provides the only method for investigating the influence of solely conformational differences upon the biochemical/biophysical properties of peptides. The significant differences in permeability and target binding affinity between the peptide diastereomers demonstrate the importance of helical conformation.

Silver catalyzed synthesis of 4-trifluoromethyl substituted quinolines in water

Herein we report the first silver catalyzed fluorinated quinoline synthesis via a cascade alkyne–ketone–amino coupling/addition/condensation process in water.

An in-tether sulfilimine chiral center induces β-turn conformation in short peptides

A sulfilimine chiral center in the tether at i, i + 3 positions of short peptides was systematically studied to elucidate the chirality-driven conformational changes. A rare and unexpected type III β-turn structure was induced in short peptides by an in-tether chiral center, supported by circular dichroism spectroscopy, NMR and X-ray crystallography.

Chiral Sulfoxide-Induced Single Turn Peptide α-Helicity

Inducing α-helicity through side-chain cross-linking is a strategy that has been pursued to improve peptide conformational rigidity and bio-availability. Here we describe the preparation of small peptides tethered to chiral sulfoxide-containing macrocyclic rings. Furthermore, a study of structure-activity relationships (SARs) disclosed properties with respect to ring size, sulfur position, oxidation state, and stereochemistry that show a propensity to induce α-helicity. Supporting data include circular dichroism spectroscopy (CD), NMR spectroscopy, and a single crystal X-ray structure for one such stabilized peptide. Finally, theoretical studies are presented to elucidate the effect of chiral sulfoxides in inducing backbone α-helicity.

Constructing thioether-tethered cyclic peptides via on-resin intra-molecular thiol-ene reaction.

Thiol–ene reactions have been used in a variety of applications that mostly involve an inter‐molecular pathway. Herein, we report a facile method to construct thioether‐tethered cyclic peptides via an intra‐molecular thiol–ene reaction. This reaction is efficient, selective, and has good residue compatibility. Short peptides with thioether tethers were constructed and were used to construct longer cyclic peptides. This synthetic method may be useful for constructing bioactive peptides. Copyright

Peptides-Staple Method Development and Its Application in Cancer Therapy

α-Helixes are important structural motifs of protein three dimension structures and are largely involved in protein- protein interactions. This review covers the recent advances of the peptide stabilizing methodologies and introduces their applications in cancer research.

Genetically encoded fluorescence screening probe for MgrA, a global regulator in Staphylococcus aureus

Herein, we construct a novel cell-based fluorescence response screening system based on a single insertion of circularly permuted yellow fluorescent protein (cpYFP) to reflect the protein conformational change caused by MgrA–small molecules interaction. And this screening platform was applied for screening of Chinese herb extracts with two extracts identified from 351.