Home > Archive for Research Progress

Li group published article on Organic & Biomolecular Chemistry about a study of Improving cell penetration of helical peptides stabilized by N-terminal crosslinked aspartic acids

Cell penetration and nucleus translocation efficiency are important for the cellular activities of peptide therapeutics. For helical peptides stabilized by N-terminal crosslinked aspartic acid, correlations between their penetration efficiency/nucleus translocation and physicochemical properties were studied. An increase in hydrophobicity...

Li group published article on Journal of Medicinal Chemistry about a study of structural basis of inhibition of ERα-coactivator interaction by high affinity N‑terminus isoaspartic acid tethered helical peptides

Direct inhibition of the protein−protein interaction of ERα and its endogenous coactivators with a cell permeable stabilized peptide may offer a novel, promising strategy for combating ERα positive breast cancers. Here, we report the cocrystal structure of a helical...

Li group published cover paper on Theranostics

Link: http://www.thno.org/v07p4566.pdf Abstract: Inhibition of the interaction between p53 and MDM2/MDMX has attracted significant attention in anticancer therapy development. We designed a series of in-tether chiral center-induced helical stabilized peptides, among which MeR/PhR effectively reactivated p53. The activation of p53...

Li group published article on Angew Chem Int Ed about a study of an in tether chiral center modulates the helicity cell permeabilityand 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...

Li group published article on The Chemical Record about a review of Thioether-Derived Macrocycle for Peptide Secondary Structure Fixation

Recently, we developed methods to stabilize peptides into various secondary structures, including a-helix, type III turn and b-hairpin via proper thioether based macrocyclization. These conformationally constrained peptidomimetics confer enhanced biophysical properties and provide a valuable avenue towards clinically-relevant therapeutic...

Li group published article on Chem Sci about a study of stapling of unprotected helical peptides via photo induced intramolecular thiol yne hydrothiolation

Peptide stapling emerged as a versatile strategy to recapitulate the bioactive helical conformation of unstructured short peptides in water to improve their therapeutic properties in targeting intracellular “undruggable” targets. Here, we describe the development of photo-induced intramolecular thiol–yne macrocyclization...

Li group published article on Acs Chemical Biology about a study of development of stabilized peptide-based PROTACs against estrogen receptor α

Peptide modulators targeting protein-protein interactions (PPIs) exhibit greater potential than small-molecule drugs in several important aspects including facile modification and relative large contact surface area. Stabilized peptides constructed by variable chemistry methods exhibit improved peptide stability and cell permeability...

Li group published article on Nano Research about a study of A simple and novel method for the quantitative detection of 5-hydroxymethylcytosine using carbon nanotube field- effect transistors.

Li group published article on Nano Research about a study of A simple and novel method for the quantitative detection of 5-hydroxymethylcytosine using carbon nanotube field- effect transistors.   5-hydroxymethylcytosine (5-hmC) is an important epigenetic derivative of cytosine and quantitative...

Li group published article on Synlett about a study of lipid–cell-penetrating-peptide conjugates as effective delivery systems

A lipid–cell-penetrating-peptide (CPP) conjugate was designed to deliver cargoes with poor cellular permeability, including peptides or small-molecule therapeutics, into cells. The lipid–CPP conjugate facilitated the cellular uptake of cargoes noncovalently through an ATP-dependent micropinocytosis mechanism. This delivery system is...

Li group published article on Chemical Communication about a study of N terminal N-methylation modulates chiral centre induced helical (CIH) peptides’ biophysical properties

The N-methylation effects on CIH peptides’ biophysical properties were systematically studied. The N-methylation at the N terminal NH could help improve the peptides’ cellular uptakes with retained helical conformation. This Nmethylation strategy could also be applied to longer peptides...

Li group published article on Chembiochem. about a study of A Thioether-Stabilized d-Proline–l-Proline-Induced β-Hairpin Peptide of Defensin Segment Increases Its Anti-Candida albicans Ability

Li group published article on Chembiochem. about a study of A Thioether-Stabilized d-Proline–l-Proline-Induced β-Hairpin Peptide of Defensin Segment Increases Its Anti-Candida albicans Ability   We report a β-hairpin dual stabilizing strategy: a d-proline-l-proline (d-Pro-l-Pro) dipeptide as the nucleating turn,...